Mechanistic insights into traditional Chinese medicine for digestive tract cancers: implications for gastric, hepatic, esophageal, intestinal, and pancreatic tumors

Yong-fu Zhu; Chang Liu; Ya-dong Wang; Jing Xu; Jia Ma; Hao Zhang; Peng-cheng Zhang; Dong-wei Zhang; Li-ming Xia; Hang Song; Xing-xing Huo

doi:10.1515/oncologie-2024-0340

Article Open Access

Mechanistic insights into traditional Chinese medicine for digestive tract cancers: implications for gastric, hepatic, esophageal, intestinal, and pancreatic tumors

Yong-fu Zhu , Chang Liu , Ya-dong Wang , Jing Xu , Jia Ma , Hao Zhang , Peng-cheng Zhang , Dong-wei Zhang , Li-ming Xia , Hang Song and Xing-xing Huo

Published/Copyright: November 13, 2024

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From the journal Oncologie Volume 26 Issue 6

Abstract

The increasing incidence of cancer-related deaths highlights the pressing need for effective treatment modalities, particularly in the context of digestive tract cancers, such as gastric, hepatic, esophageal, intestinal, and pancreatic tumors. While conventional drug therapies play a critical role in managing these malignancies, their associated side effects often pose significant challenges to patient quality of life. Thus, there is a growing focus on traditional Chinese medicine (TCM) and its compounds, which are safe, non-toxic, and reliable. During anti-tumor therapy, TCM compounds, based on their multi-target, multi-pathway, and multi-level regulatory effects, fully mobilize multiple mechanisms of the body, presenting significant advantages in inhibiting tumor development, boosting patient welfare, and increasing their lifespan. This article reviews the mechanisms by which TCM inhibits tumor cell proliferation, promotes tumor cell death, suppresses tumor cell invasion and metastasis, regulates the tumor microenvironment, inhibits angiogenesis, and enhances anti-tumor drug resistance. This knowledge might provide a theoretical and scientific basis for preventing and treating tumors using TCM.

Keywords: Chinese medicine; Chinese medicine compound; natural products; digestive tract; anti-tumor; mechanism

Introduction

Digestive system tumors, including esophageal, gastric, intestinal cancer, and liver cancers, remain a significant health challenge worldwide with high morbidity and mortality rates [1, 2]. Traditional interventions such as surgical operations, chemotherapy, and radiotherapy have demonstrated constrained effectiveness in dealing with these tumors, frequently associated with harsh side effects and an elevated risk of recurrence. Therefore, there is a growing interest in alternative and complementary treatments to improve the prognosis for individuals battling gastrointestinal cancers. Traditional Chinese Medicine (TCM) has been increasingly recognized for its potential in the management of various types of cancer, including digestive tract tumors [3]. TCM offers a holistic and personalized approach to cancer care, targeting not only the tumor itself but also the overall well-being of the patient.

In the realm of cancer treatment, formulations derived from TCM exhibit regulatory actions across multiple targets, pathways, and levels, which can fully mobilize various mechanisms of the body, thus having significant advantages in inhibiting the tumor process, improving patients’ quality of life, and prolonging patients’ survival [4, 5]. However, the complex composition of TCM formulas is also the main reason why it is difficult for the international community to fully understand.

As is widely known, there have been significant advances in the application of TCM for the management of the digestive tract and have reported promising outcomes in terms of tumor regression, symptom alleviation, and quality of life improvement in patients receiving TCM interventions alongside conventional treatments. The action of TCM components, like anti-inflammatory, immunomodulatory, and anti-angiogenic properties, have contributed to the growing interest in integrating TCM into mainstream cancer care 6], [7], [8], [9.

This article reviews the mechanisms by which TCM inhibits tumor cell proliferation, promotes tumor cell apoptosis, suppresses tumor cell invasion and metastasis, regulates the tumor microenvironment, inhibits angiogenesis, and enhances anti-tumor drug resistance, as shown in Figure 1. This knowledge might provide a theoretical and scientific basis for preventing and treating tumors using TCM. The purpose is to provide the theoretical basis for TCM in the prevention and treatment of tumors and to offer insights for subsequent research endeavors.

Figure 1:

Comprehensive illustration of research framework and results: (A) graphical abstract; (B) flow chart; the figures were created using BioRender (www.biorender.com).

Anti-tumor active components

Modern pharmacology demonstrates that TCM herbs contain numerous anti-tumor active components, including flavonoids, alkaloids, polysaccharides, terpenoids, phenols, and saponins [10, 11]. As shown in Table 1, Rubus idaeus is rich in anthocyanins; Glycyrrhiza glabra is rich in isoliquiritigenin; Astragalus mongholicus is rich in astragalus polysaccharide and astragaloside; Scutellaria baicalensis is rich in wogonin and baicalin; Panax ginseng is rich in ginseng polysaccharide and ginsenoside; Artemisia carvifolia is rich in artesunate, dihydroartemisinin, and other chemical components that have been proven to effectively prevent tumor progression 12], [13], [14], [15], [16], [17], [18.

Table 1:

Active components of TCM and their mechanisms of action.

Class	Chemical name	Source of medicinal materials	Tumor type	Mechanism(s) of action	Reference
Flavonoid	Anthocyanidin	Rubus idaeus	Colorectal cancer (CRC)	Prevention of CRC development in a mouse model	[23]
	Isoliquiritigenin	Glycyrrhiza glabra	Colitis-associated tumors	Blocks M2 macrophage polarization in colitis-associated tumorigenesis through downregulating PGE2 and IL-6	[24]
	Dihydrosalicylate	Nekemias megalophylla	Hepatocellular carcinoma (HCC)	Promoted HCC regression through a p53 activation-dependent mechanism	[25]
	Kaempferol	Kaempferia galanga	Pancreatic cancer	Induction of ROS-dependent cell apoptosis in pancreatic cancer cells by TGM2-mediated Akt/mTOR signaling	[26]
	Quercetin	Fruit and vegetable	Various tumors	The ability to regulate PI3K/Akt/mTOR, Wnt/catenin, and MAPK/ERK1/ERK2 pathways to promote loss of cell viability, apoptosis, and autophagy	[27]
	Baicalin	Scutellaria baicalensis	Colon carcinoma	Tumor cell senescence by upregulating DEPP and activation of Ras/Raf/MEK/ERK signaling	[28]
	Daidzein	Glycine max	Liver cancer	Inhibition of hepatocarcinogenesis by cell cycle arrest, inhibition of proliferation by inhibition of Ki-67 expression, and induction of Bcl-2-mediated apoptosis	[29]
	Icariin	Epimedium sagittatum	Gastric cancer (GC)	Inhibition of gastric cancer cell growth by modulation of the hsa_circ 0003159/miR-223-3p/NLRP 3 signaling axis	[30]
	Cardamom ming	Alpinia hainanensis	CRC	Inhibition of migration, invasion, EMT, and lung metastasis of CRC cells by downregulation of ADRB 2 expression	[31]
	Wogonin	Scutellaria baicalensis	Carcinoma of colon	The Hippo signaling pathway mediated by IRF 3 alleviates the oncogenic behavior and EMT in colon cancer cells	[32]
	Luteolin	Reseda odorata	Esophageal cancer	To attenuate cancer cell stemness in PTX-resistant oesophageal cancer cells by mediating SOX 2 protein stability	[33]
	Wogonoside	Scutellaria baicalensis	GC	Promote apoptosis and ER stress in human gastric cancer cells by regulating the IRE 1 α pathway	[34]
	Naringenin	Anacardium occidentale	Liver cancer	Inhibit the growth of HCC cells by inhibiting cell proliferation and inducing apoptosis	[35]
Alkaloids	Matrine	Sophora flavescens	Pancreatic cancer	Growth inhibition of KRAS mutant pancreatic cancer via autophagy-mediated energy metabolism inhibition	[36]
	Ligustrazine	Conioselinum anthriscoides ‘Chuanxiong’	GC	Induction of apoptosis in GC cells via ROS/AMPK pathway activation	[37]
	Betaine	Beta vulgaris	Liver cancer	Affects p16 and c-myc DNA methylation and mRNA levels in a chemically induced rat liver cancer model	[38]
	Homoharringtonine	Cephalotaxus harringtonia	CRC	Inhibits CRC progression via PI3K/AKT/mTOR signaling pathway inactivation	[39]
	Capsaicin	Capsicum annuum	HCC	Participates in the autophagy and apoptotic pathway in HCC	[40]
	Cepharanthine	Stephania japonica	HCC	Suppresses the expansion and multiplication of liver cancer cells by modulating amino acid processes	[41]
	Sinomenine	Stephania tetrandra	GC	Sensitizes GC cells to 5-fluorouracil	[42]
	Berberine	Coptis chinensis	Colon carcinoma	Inhibition of colon cancer cell proliferation by inhibiting lipogenesis mediated by the SCAP/SREBP-1 signaling pathway	[43]
	Vincristine	Catharanthus roseus	Colon carcinoma	Low DBN1 gene expression might be related to the resistance of colon cancer cells to vincristine	[44]
	Sanguinarine	Chelidonium majus	Pancreatic cancer	Inhibition of pancreatic cancer stem cell signature by induction of oxidative stress and inhibition of the Shh-Gli-Nanog pathway	[45]
Polysaccharide	Ginseng polysaccharide	Panax ginseng	GC	Induction of apoptosis by targeting the Twist/AKR1C2/NF-1 pathway in GC	[46]
	Dendrobium polysaccharide	Dendrobium	Colon carcinoma	Induction of colon cancer cell death through the ROS-AMPK-autophagy pathway	[47]
	Lycium barbarum polysaccharide	Lycium barbarum	GC	Contributes to the antitumor effect against stomach cancer cells by triggering a halt in the cell cycle	[48]
	Astragalan	Astragalus mongholicus	GC	Boosts the tumor-suppressive impact of apatinib on gastric adenocarcinoma AGS cells through the suppression of the AKT signaling cascade	[49]
	Rhubarb polysaccharides	Rheum rhabarbarum	Radiation enteritis	Significant ameliorated radiation-induced intestinal damage by regulating Nrf 2 and its downstream protein HO-1	[50]
	Barley polysaccharide	Hordeum vulgare	Colon carcinoma	Induction of colon cancer HT-29 apoptosis by the caspase pathway mediated by ROS-JNK and NF-κB	[51]
Terpene	Andrographolide	Andrographis paniculata	Colon carcinoma	Promotes programmed cell death in human colon cancer cells via the initiation of the ROS-dependent JNK signaling pathway	[52]
	Ganoderma lucidum acid	Ganoderma lucidum	Colon carcinoma	Energy reprogramming influences on colon cancer mediated by SIRT 3 upregulation through acetylation of CypD inhibition	[53]
	Geun-leather acetic acid	Pseudolarix amabilis	Liver cancer	Triggered programmed cell death and halted the cycle in HCC cells	[54]
	Artesunate	Artemisia carvifolia	Colon carcinoma	Promotes apoptosis and autophagy in colon cancer cells	[55]
	Dihydroartemisinine	Artemisia carvifolia	Liver cancer	Triggers iron death in primary HCC cells via CHAC1 upregulation by promoting and unfolding protein responses	[26]
	Paclitaxel	Taxus wallichiana	GC	MiR-200a and FH535 can amplify the suppressive effects of paclitaxel on the proliferation of GC cells	[56]
	Malol	Prunella vulgaris	GC	Silencing of CYP19A1/aromatase inhibits GC growth	[57]
	Triptolide	Tripterygium wilfordii	GC	The antigastric cancer effect of triptolide is related to the H19/NF-κB/turn axis	[58]
Phenols	Dehydroeffusol	Juncus effusus	GC	Suppresses tumor growth and tumorigenesis by substantial induction of tumor ER stress response and moderate activation of apoptosis	[59]
	Curcumin	Curcuma longa	Various tumors	Cell signaling pathways involved in cancer development and proliferation, and cell signaling pathways targeted by curcumin	[60]
	Large leaf lacphenolic	Dendrobium	Liver cancer	Attenuates the proliferation of human hepatoma cells through the PI3K/Akt/NF-κB signaling pathway	[61]
	Resveratrol	Vitis vinifera	Various tumors	Regulation of apoptosis and autophagy as the major form of cancer cell death by targeting various signaling pathways and up/downregulation of apoptosis and autophagy genes	[62]
Saponins	Saikoside	Bupleurum falcatum	Liver cancer	Inhibition of primary liver cancer by regulating the STK4/IRAK1/NF-κB pathway	[63]
	Astragaloside IV	Astragalus mongholicus	Liver cancer	Regulation of macrophage polarization by the TLR4/NF-κB/STAT3 signaling pathway to inhibit HCC progression	[64]
	Ginsenoside	Panax ginseng	Gastroenteric tumor	Inhibits tumor progression by regulating autophagy, apoptosis, proliferation, migration, and angiogenesis	[65]
	Dioscin	Dioscorea polystachya	GC	Effectively inhibits the proliferation of GC	[66]

A wealth of research indicates that TCM exerts anti-tumor effects through a variety of pathways involving multiple targets, such as modulating cell signal transduction, thereby effectively inhibiting the excessive proliferation of cancer cells [19]. As shown in Figure 2, TCM has numerous active ingredients, including flavonoids (e.g., anthocyanins, isoliquiritigenin, dihydromyricetin, kaempferol, quercetin, baicalin, daidzein, icariin, cardamoni, wogonin, wogonoside, luteolin, and naringenin); alkaloids (e.g., matrine, ligustrazine, betaine, homoharringtonine, capsaicin, cepharanthine, sinomenine, berberine, vincristine, and sanguinarine); polysaccharides from, for example, P. ginseng, Artemisia argyi, Dendrobium, Cichorium intybus, Lycium barbarum, Hippophae rhamnoides, Conioselinum anthriscoides ‘Chuanxiong’, Portulaca oleracea, pomegranate peel, Eleutherococcus giraldii, Astragalus mongholicus, Platycodon grandiflorus, Rheum rhabarbarum, and Hordeum vulgare; terpenoids (e.g., andrographolide, ganoderma acid, pseudolaric acid B, dehydrorosin acid, artesunate, dihydroartemisinin, paclitaxel, cajuputene, pristimerin, ursolic acid, triptolide, and ginseng triterpenes); phenols, including dehydroeffusol, curcumin, dendrophnol, and resveratrol; and saponins, such as saikoside, Astragalus saponin, amarogentin, ginsenoside, and potato saponins [11, 20]. See Table 1 for further details. Additionally, combining multiple active ingredients and chemotherapeutic drugs offers significant advantages in reversing tumor multidrug resistance [21]. For instance, the combination of curcumin and FOLFOX chemotherapy (leucovorin/1-fluorouracil/oxaliplatin) was found to be both well-tolerated and safe for patients with metastatic colorectal cancer (CRC), exhibiting no substantial differences in regard to life quality or neurotoxicity [22].

Figure 2:

TCM has numerous active ingredients: including flavonoids; alkaloids; polysaccharides; terpenoids; phenols and saponins. The figures were created using BioRender (www.biorender.com).

Anti-tumor mechanisms of TCM compounds

TCM formulations are extensively utilized in the treatment of diverse ailments, including cancer. Records of tumor treatment can be found in the “Classified Materia Medica” and “Puji Prescription”. Zhang Xichun’s book “Records of Chinese Medicine with Reference to Western Medicine” proposed the concept of tumor treatment, which involves replenishing Qi, attacking and reinforcing, and protecting the dirty gas [67]. TCM compounds are valuable and are characterized by complex chemical compositions, pharmacological targets, multi-level and multi-link actions, and various dosage forms. Compound cancer treatment guided by TCM theory includes eliminating pathogenic heat, enhancing blood flow, and dispelling blood obstructions, upright culture, Qi Yin, soft powder, and poison. With the advancements in modern science and technology and the deepening of research, the scientific mechanism of TCM compound cancer treatment has gained increasing attention. As shown in Figure 3, the popular phosphatidyl inositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling, epidermal growth factor receptor (EGFR), p53, Wnt, Janus kinase-signal transducer and activators of transcription pathway (JAK-STAT), transforming growth factor-β (TGF-β), and nuclear factor-κB (NF-κB) pathway have been implicated in the proliferation and control of tumor cells. See Table 2 for further details. Among them, the PI3K/Akt/mTOR signaling pathway is crucial in tumor signaling, and targeting the mTOR signaling pathway has emerged as a focal point for tumor treatment research and development [68]. EGFR can activate downstream signaling pathways and regulate various physiological processes such as cell growth and proliferation. Many solid tumors have somatic mutations or abnormal expression of genes related to the EGFR signaling pathway, which are closely associated with tumor growth, invasiveness, and metastasis [69]. Additionally, p53-mediated cell signaling pathways are complex and are essential for preserving the normal physiological processes of cells.

Figure 3:

The mechanism of action of traditional Chinese medicine compound in cancer treatment. Chinese medicine compounds: (A) Ziyin Huatan recipe; (B) Kushen injection; (C) compound lizard powder gel; (D) Shougong powder; (E) Da Chaihutang; (F) Yinchenhao decoction; (G) Zangduqing; (H) Si Junzitang; (I) Xiangsha Liujunzi decoction; (J) Banxia Xiexin Tang; (K) Xuefu Zhuyu decoction; (L) Da Huang Mu Dan Tang; (M) Zuojin pills; (N) Qingyihuaji formula, etc. The figures were created using BioRender (www.biorender.com).

Table 2:

Composition of TCM compounds and their anti-tumor mechanisms.

Tumor	Compound	Genes/proteins involved	Mechanism(s) of action	Reference
GC	Ziyin Huatan Recipe	RUNX3	Inhibition of GC migration and invasion via RUNX3 upregulation	[86]
	Wumei San	Cox-2, PGE2, PI3K, AKT, GSK3β, β-catenin	Inhibit the invasion and metastasis of GC by downregulating expression of Cox-2/PGE2	[102]
	Kushen injection	PI3K, AKT	Inhibition of EMT progression in GC cells via the PI3K/AKT pathway	[82]
	Jianpi Yangzheng Xiaozheng decoction	EMT	Inhibition of EMT progression in GC	[92]
	Modified Jian-pi-yang-zheng decoction	PI3Kγ, IL-10, TNF-α, IL-1β	Inhibition of EMT in GC cells by PI3Kγ-dependent TAM	[91]
	Xiaotan Sanjie decoction	IL-8, VEGF, Notch-1	VEGF pathway regulation suppresses GC angiogenesis by IL-8 and attenuates tumor angiogenesis by manipulating Notch-1-regulated GC stem-like cell proliferation	[94, 95]
	Compound lizard powder gel	PI3K, AKT, mTOR	Treatment of preGC is effective and probably related to the PI3K/AKT/mTOR signaling pathway	[103]
	Fupi Hualiu decoction	Bax, Bcl-2	Induction of apoptosis and associated apoptotic gene expression in GC mice	[104]
	Banxia Xiexin decoction	PI3K-Akt, MAPK, NF-κB	It involves cell apoptosis, proliferation, and regulation of the tumor microenvironment and the internal body environment and participates in the proliferation, apoptosis, neuroendocrine immunity, and other mechanisms to play an anti-gastric cancer role	[105]
Liver cancer	Shougong powder	XPA, XPC, Rad23B, RPA14, RPA32, RPA70, ERCC1	Inhibits the malignant phenotype of HCC cells by targeting the DNA damage repair pathway	[81]
	Jiedu Xiaozheng Yin	HIF-1α, GLUT-1, HK, PFK, MCT-4, miR-210	Inhibits HIF-1/miR-210 expression, inhibiting the key enzymes of glucose metabolism and glycolytic capacity of HCC cells, as well as proliferation, invasion, and metastasis	[106]
	Da Chaihutang	IL-6, IL-1β, TNF-α, MAPK, STAT3	Inhibits the activity of HCC by regulating the p38 MAPK/IL-6/STAT3 signaling axis	[107]
	Yinchenhao decoction	AKR1D1, CYP2C9, CYP2E1, CYP3A4, and SLC22A7	The inflammatory signaling pathway and metabolic pathway are the most critical pathways through which YCHD provides anti liver cancer effects	[108]
	Modified Yinchenhao decoction	Caspase-3, Caspase-9, Bax, Bcl-2, Bcl-x	Inhibits subcutaneous graft tumor growth in human HCC nude mice via induction of tumor cell apoptosis by the activated mitochondrial pathway	[109]
	Fuzheng Yiliu decoction	Beclin-1, LC3, Bnip3	Inhibits the growth and enhances the autophagic activity of human hepatoma Hu-7 transplanted tumor cells	[110]
	Compound Songyou Yin	MTSS1, Caspase-3	Induces apoptosis in HCC cells may be associated with the inhibition of MTSS 1 gene expression and Caspase-3 activation	[111]
	Gupi Xiaoji decoction	MDA, Bax, Bcl-2, Caspase-3	Induction of apoptosis affecting the energy metabolism	[112]
	Qiye Baogan decoction	DPPH radical	It has strong antioxidant activity and can inhibit the growth of Hep G2 HCC cells and promote their apoptosis	[113]
Intestinal cancer	Cerebiogen capsule	MVD, VEGF, VEGFR2	Intervention in colon cancer angiogenesis through the VEGF/VEGFR2 signaling pathway	[114]
	Zangduqing	Caspase-3, Caspase-9, Bax, Bal-2	Human colon cancer cell apoptosis through the mitochondrial apoptosis pathway	[115]
	Tenglong Buzhong decoction	IFN-γ, IL-12	Improves the immune function of CRC tumor-bearing mice and stimulates the Th1 type immune response	[116]
	Si Junzitang	NKG2A, IL-15, HLA-E	Inhibition of NKG2 A-HLAE pathway signaling activation, restoring NK cell anti-colon cancer effects	[117]
	Dahuang Mudan decoction	PPAR, p53, and other signaling pathways	Therapeutic effects on CRC relate to multi-level, multi-pathway, and multi-target sites	[118]
	Xiangsha Liujunzi decoction	Bax, Caspase3, Bcl-2, p-PI3K, PI3K, p-Akt, Akt, Bcl-2, Bax, Capase3	Inhibits tumor growth in colon cancer tumor-bearing nude mice; the mechanism might be related to apoptosis induction	[119]
	Fuzheng Shengbai decoction	CD4+, CD4+/CD8+, IgA, IgG, IgM, miR-124	It can effectively control chemotherapy-induced leukopenia in CRC and improve the efficacy of chemotherapy by reducing miR-125b and increasing miR-124 expression	[120]
	Banxia Xiexin decoction	bFGF, Ang-2, VEGF, VEGFR2	Inhibits graft tumor growth and destroys the tumor tissue growth microenvironment in colon cancer nude mice	[121]
	Modified Sijunzi decoction	CD68, CD206	Inhibits tumor growth, and the mechanism of action might be related to CD68 and CD206 downregulation in tumor-associated macrophages	[122]
Esophageal cancer	Coptis decoction	JUN, RELA, TP53, TNF, MAPK1, FOS	Play the inhibitory effect of oesophageal cancer through signaling pathways such as MAPK	[123]
	Kushen injection	VEGF, bFGF, PI3K, p-PI3K, Akt, p-Akt	Inhibits tumor growth in esophageal cancer model rats by downregulating the PI3K/Akt signaling pathway	[124]
	Shashen Maidong decoction, and Tongyou decoction	Caspase-3, FADD, Fas, TNFR1, DR5	Induction of apoptosis via activation of Caspase-3, FADD independent/dependent death receptor pathways, and upstream signaling pathways related to other apoptotic proteins	[125]
	Qigesan, Shashenmaidongtang, Tongyoutang, and Buqiyunpitang	EGFR, PLC-γ1, PKCα, MARCKS, PI3K, AKT-1	Differential inhibition of hEGF-stimulated esophageal cancer cell growth through the inhibition of growth signaling mediated by PLC- γ1 and PI3K	[126]
	Banxia Xiexin Tang	STAT3	It affects the regulation point of the esophageal cancer cell cycle and promotes the apoptosis of tumor cells	[127]
Pancreatic cancer	Prescription of detoxication of dryness-dampness	APP, PLK1, PPARG, CA2	Subcutaneous tumor-bearing model of inhibitory mouse pancreatic cancer cell lines	[128]
	Da Huang Mu Dan Tang	ALT, AST, BUN, Cr, TBiL	Promotes tumor cell apoptosis and can protect the liver and kidney function of pancreatic cancer rats	[129]
	Zuojin pills	PI3K-AKT, IL-17, TNF, HIF-1, P53	Significantly inhibits cell cycle and proliferation and induces apoptosis through the PI3K/AKT/caspase pathway	[130]
	Qingyihuaji formula	PI3K/AKT/mTOR, Keap1/Nrf2/HO-1, Bcl2/Bax	Inhibits the growth and progression of pancreatic cancer via several mechanisms, including anti-inflammatory mechanisms and apoptosis induction	[88]
	Qingyihuaji formula	CASP3, SRC, STAT1, PTPN11, PKM, PAK1	Activates STAT1, inhibiting MAPK/ERK and PI3K/Akt/mTOR signaling pathways in vitro and in vivo	[131]
	Qingyihuaji formula	lncRNA AB209630/miR-373/EphB2-NANOG	Reverses gemcitabine-resistant human pancreatic cancer by regulating lncRNA AB209630/miR-373/EphB2-NANOG signaling	[132]
	Xiang-lian pill	PTGS1, PTGS2, KCNH1, PRSS90, HSP1AA5	PTGS2-mediated inhibition of MEK/ERK is a key therapeutic mechanism for Xianglian bolus	[133]

In the complex and intricate network of tumor formation, p53 represents a crucial breakthrough in achieving personalized tumor therapy [70]. Abnormal Wnt pathway activation is also closely associated with cancer initiation [71]. The TGF-β family plays a vital role in various cellular activities, such as proliferation, apoptosis, invasion, metastasis, extracellular matrix remodeling, differentiation, and immune regulation. Dysfunctional TGF-β signaling pathways are closely related to the development of tumors by disrupting cellular physiology [72]. The NF-κB family is a group of transcription factors with multiple physiological functions, playing a critical role in immunity, inflammatory response, cell differentiation, growth, and survival. Enhanced NF- κB signaling pathway activity has been discovered in several cancers. High expression or mutation of the NF-κB signaling pathway can result in persistent pathway instigation, fostering tumor development and progression [73].

Proliferation inhibition of tumor cells and apoptosis promotion

The proliferative properties of tumor cells are not limited by density dependence, and when proliferation reaches a certain stage, they can invade and destroy surrounding normal tissue cells and even metastasize to other organs and tissues to form secondary tumors. Zuojin capsule is a compound preparation traditionally used for burning the stomach and has inhibitory effects on CRC. The mechanisms of action might be related to the targeting of several candidate genes, including cyclin-dependent kinase inhibitor 1A (CDKN1A), B-cell lymphoma 2 (Bcl2), E2F transcription factor 1 (E2F1), protein kinase C-alpha (PRKCB), myelocytomatosis oncogene (MYC), Cyclin-dependent kinase 2 (CDK2), and Matrix Metalloproteinase-9 (MMP9) [74]. Similarly, the Zuojin capsule has also shown promise in treating CRC by targeting AKT 1, Jun proto-oncogene (JUN), CDKN1A, B-cell lymphoma-2 like 1 (BCL2L1), and nuclear receptor coactivator 1 (NCOA1). The PI3K-AKT signaling pathway might play an important role in the treatment of CRC [75]. In a CRC mouse model, the TCM compound Pien Tze Huang impairs tumor cell proliferation and stimulates cell apoptosis by inhibiting the signal transducer and activator of transcription 3 (STAT3) pathway [76].

Additionally, Sanjie Yiliu Formula substantially reduced the viability of numerous CRC cell lines, encompassing human ileocecal adenocarcinoma (HCT-8), human colorectal carcinoma cells (SW-480), human colon carcinoma (HT-29), and human colon adenocarcinoma cells (DLD-1), while leaving the normal human renal cell line (HK-2) unaffected. This inhibitory effect was associated with decreased expression of cyclin D1, cyclin-dependent kinase (CDK4), and BCL-2, coupled with elevated levels of Bcl-2-associated X protein (Bax) at both mRNA and protein levels [77]. Yang et al. demonstrated that Qingjie Fuzheng granules inhibited CRC cell growth by modulating the PI3K/Akt and extracellular signal-regulated kinase (ERK) pathways [78]. Subsequent studies also partially validated the therapeutic effects of Qingjie Fuzheng granules. Zhu et al. discovered that the elimination of granules could inhibit the proliferation of CRC cells and promote apoptosis, as well as tumor angiogenesis, through the inhibition of the Sonic hedgehog (SHH) pathway [79]. Huang et al. found that Qingjie Fuzheng granules could curb the viability, migration, invasion, and tube formation of CRC cells while inducing hetero-lymphangiogenesis in CRC via the vascular endothelial growth factor-C (VEGF-C)/vascular endothelial growth factor receptor-3 (VEGFR-3)-dependent PI3K/Akt pathway [80]. These findings serve as a valuable instrument for advancing ethnomedicine research in the treatment of intractable diseases.

Inhibition of tumor cell invasion and metastasis

Cancer cells exploit two distinct but related processes - invasion and metastasis - to infiltrate local tissue and spread to distant sites. Tissue invasion enables tumor cells to extend beyond their primary location. Metastasis refers to the process whereby tumor cells depart from the primary site, relocate to new positions, and establish secondary tumors in a novel environment. These complex processes leverage existing cellular mechanisms to achieve tumor cell invasion and migration, including adherens junction signal transduction pathways.

Studies have also demonstrated the anti-tumor effects of TCM compounds. Recent studies have shown that Shougong powder can inhibit the proliferation and metastasis and induce apoptosis of hepatocellular carcinoma (HCC) cells by regulating the DNA damage repair pathway [81]. Kushen injection inhibited the growth and migration of gastric cancer (GC) cells, induced apoptosis, and regulated the epithelial-to-mesenchymal transition (EMT) process via the PI3K/AKT signaling pathway. The key gene responsible for these effects is AKT1 [82].

JianPi JieDu Recipe presents another promising alternative for preventing and treating CRC. It can inhibit the invasion and migration ability of TGF-β-stimulated CRC cells by upregulating E-cadherin and Smad 2/3 in the cytoplasm and downregulating Vimentin, p-Smad 2/3, and Snail CRC tissues in situ [83].

Pien Tze Huang, a renowned TCM prescription, can also inhibit liver metastasis by targeting TGF-β signaling in a CRC liver metastasis mouse model. In addition, it inhibited human CRC cell metastasis by regulating the TGF-β1/Zinc-finger enhancer binding (ZEB)/miR-200 signaling network [84, 85].

TCM compounds have also demonstrated significant therapeutic value in treating gastric and pancreatic cancers. Network pharmacological analysis suggests that Ziyin Huatan Recipe is promising for treating GC. By inhibiting the proliferation and invasion of cancer cells and modulating the expression of metastasis-related targets, it can suppress GC progression. The underlying biological processes may involve the enhancement of Runt-related transcription factor 3 (RUNX3) expression [86].

Weichang’an can inhibit the progression of GC cells. It can inhibit the triggering of the Wnt/β-catenin pathway, thereby limiting cell movement and invasion [87]. Another promising treatment for pancreatic cancer is the pancreatic formula, which has shown significant clinical efficacy. It suppresses cell multiplication, infiltration, and motility, and promotes apoptosis in vitro. This formula downregulates intercellular adhesion molecule 1 (ICAM1), vascular cell adhesion molecule 1 (VCAM1), and Bcl-2 mRNA levels and upregulates heme oxygenase 1 (HO-1) and NAD(P)H: quinone oxidoreductase 1 (NQO1). Immunoblotting has also shown significant changes in the PI3K/AKT/mTOR, Kelch-like ECH-associated protein 1 (Keap1)/NF-E2-related factor 2 (Nrf2)/HO-1/NQO1, and Bcl-2/Bax pathways after treatment with the pancreatic formula. The pancreatic formula can impede the growth and advancement of pancreatic cancer via various mechanisms, such as anti-inflammatory actions and the triggering of apoptosis [88].

Regulation of the tumor microenvironment

Scholars have long believed that tumors are not just a mass of single tumor cells but a heterogeneous mixture of tumor cells, fibroblasts, immune cells, inflammatory cells, glial cells, nearby stroma cells, other cells, microvessels, and infiltrating biomolecules. Since the “tumor microenvironment” proposal in 1993, it has been recognized that the tumor process is intimately connected to the internal and external environment in which tumor cells reside. Recently, advances in molecular biology and tumor cytology have deepened our understanding of the interaction between tumors and their environment, which has positive implications for the diagnosis, prevention, treatment, and prognosis of tumors.

Moreover, the Kushen injection markedly amplifies the cancer-fighting effectiveness of sorafenib at subclinical doses without notable adverse effects. Yang et al. found that Kushen injection influences macrophages and CD8 T cells, reshaping the immune microenvironment of HCC, improving the therapeutic effect of sorafenib, and avoiding adverse reactions of chemotherapy [89].

The entry of immune cells into the hepatocellular carcinoma microenvironment primarily explains why HCC patients often experience cancer recurrence and untreated disease, with Treg cell infiltration being the main triggering factor. Dahuang Zhechong pills are a traditional herbal compound successfully used to treat hepatitis and HCC. It impedes the progression of liver cancer by adjusting the Treg/Th1 equilibrium [90].

Jian-pi-yang-zheng decoction is a TCM used to treat advanced GC and is effective for patients. A modified version of the Jian-pi-yang-zheng decoction reduced phosphoinositide 3-kinase γ (PI3Kγ) and Interleukin-10 (IL-10) activity in tumor-associated macrophages (TAMs), increased the expression of proinflammatory cytokines such as tumour necrosis factor-alpha (TNF-α) and interleukin-1β (IL-1β), and ultimately promoted the conversion of TAMs from alternatively activated type 2 (M2) to classically activated type 1 (M1), inhibiting GC growth and metastasis [91]. Similarly, the Jian-pi-yang-zheng decoction and its ingredients can prevent GC and effectively inhibit its EMT process [92].

Inspired by the Synopsis of the Golden Chamber, Zhang et al. believe that coix seed is a promising protective agent. It can prevent the formation of colorectal tumors by strengthening Treg-triggered immunosuppression, which is facilitated by hypoxia inducible factor-1 alpha (HIF-1α) [93].

Inhibition of angiogenesis

Early studies have demonstrated that tumor growth is often accompanied by an increase in vascularity, indicating that vascular proliferation might play a key role in tumorigenesis. Therefore, inhibiting tumor angiogenesis has emerged as a promising approach for controlling tumor neoangiogenesis, starving tumors, and reducing tumor growth and metastasis. The Xiaotan Sanjie decoction might inhibit angiogenesis in GC by regulating the VEGF pathway via Interleukin-8 (IL-8) [94]. Additionally, the decoction can attenuate tumor angiogenesis by manipulating Notch-1-regulated stem-like cell proliferation in GC [95].

Overcoming tumor resistance

In addition to the various anti-tumor mechanisms previously discussed, it is essential to highlight the role of TCM in addressing tumor drug resistance, a significant challenge in cancer treatment. Certain TCM compounds have demonstrated potential in reversing multidrug resistance in cancer cells, possibly by mechanisms such as the modulation of drug transporters and the apoptosis pathways. Gegen Qinlian Decoction can enhance the receptiveness of oxaliplatin-resistant CRC cells to oxaliplatin, reduce tumor volume, reduce toxic and side effects, and enhance outcomes [96]. Baicalin can heighten the responsiveness of GC cells, which are resistant to oxaliplatin, to chemotherapy by triggering p53-induced ferroptosis [97]. Lin et al. demonstrated that Gegen Qinlian Decoction reverses oxaliplatin resistance in CRC by inhibiting YTH domain family protein 1(YTHDF1)-regulated m6A modification of glutaminase 1(GLS1) [98]. Ou et al. demonstrated that Jianpi Jiedu decoction reverses 5-fluorouracil resistance in CRC by suppressing the glutamate transporter/glutathione/glutathione peroxidase (xCT/GSH/GPX4) axis to induce ferroptosis [99].

Application of TCM Compound in Treating Digestive Tract Tumors

The rising incidence and mortality rates of gastrointestinal tumors have garnered widespread attention from scholars [100, 101]. Nowadays, many experiments have confirmed that various TCM formulations have the following effects in dealing with different digestive tract tumors: directly inhibit tumor cell proliferation, promote tumor cell death, inhibit tumor cell invasion and metastasis, regulate the tumor microenvironment, inhibit angiogenesis, and enhance anti-tumor drug resistance (as detailed in Table 2).

Gastric cancer

Regarding GC, in addition to the ones mentioned earlier, Ma et al. discovered that Compound Wumei Powder can effectively inhibit the progression of GC [102]. Compound Lizard Powder Gel is a commonly used formulation in clinical practice for the treatment of GC and precancerous lesions. It may inhibit the progression of GC precursors by modulating the PI3K/AKT/mTOR signaling pathway [103]. Fupi Hualiu decoction can induce apoptosis and associated apoptotic gene expression in GC mice [104]. Research indicates that Banxia Xiexin Decoction can exert anti-GC effects involving cell apoptosis, proliferation, regulation of tumor microenvironment and in vivo environment, and participation in mechanisms such as cell proliferation, apoptosis, neuroendocrine immunity, etc. [105].

Liver cancer

We have previously confirmed that Compound Shougong powder can inhibit the HCC cells by targeting the DNA damage repair pathway [81]. Jiedu Xiaozheng Yin can inhibit HIF-1/miR-210 expression, inhibiting the key enzymes of glucose metabolism and glycolytic capacity of HCC cells, as well as proliferation, invasion, and metastasis [106]. Da Chaihutang can suppress HCC by Regulating p38 mitogen-activated protein kinase (MAPK)/IL-6/STAT3 signaling pathway [107]. Yinchenhao decoction can inhibit HCC by regulating inflammatory and metabolic pathways [108]. Modified Yinchenhao Tang can inhibit the growth of subcutaneous transplanted tumors of human liver cancer in nude mice, and its mechanism of action may be induced by activating the mitochondrial pathway. It is achieved by inducing apoptosis of tumor cells [109]. Fuzheng Yiliu Tang can inhibit the growth of tumors in nude mice transplanted with human liver cancer cells Hu-7 and enhance the autophagy activity of tumor cells [110]. Compound Songyou Yin can induce apoptosis in HCC cells, which may be associated with the inhibition of (Metastasis suppressor 1) MTSS1 gene expression and Caspase-3 activation [111]. Gupi Xiaoji decoction can induce apoptosis of human hepatoma HepG2 cells [112]. Qiye Baogan Decoction can inhibit the growth of HepG2 liver cancer, promote apoptosis of liver cancer cells, and have a certain effect on inhibiting tumor growth [113].

Intestinal cancer

Cerebiogen capsules can intervene in colon cancer angiogenesis by the VEGF/VEGFR2 signaling pathway [114]. Zangduqing capsules can induce apoptosis in human colon cancer SW480 cells [115]. Tenglong Buzhong Decoction can improve the immunological role of CRC mice with tumors and stimulate the Th1 type immune response [116]. Si Junzitang Regulates NKG2A Expression to Improve Anti-colon Cancer Function of NK Cells [117]. The therapeutic effect of Dahuang Mudan decoction on CRC involves multiple levels, pathways, and targets [118]. Xiangsha Liujunzi Decoction inhibits tumor growth in colon cancer tumor-bearing nude mice; the mechanism might be related to apoptosis induction [119]. Fuzheng Shengbai Decoction can effectively control chemotherapy-induced leukopenia in CRC and improve the efficacy of chemotherapy by reducing miR-125b and increasing miR-124 expression [120]. Banxia Xiexin Decoction can inhibit graft tumor growth and destroy the tumor tissue growth microenvironment in colon cancer nude mice [121]. Modified Sijunzi Decoction can inhibit tumor growth, and its mode of operation could possibly be associated with CD68 and CD206 downregulation in tumor-associated macrophages [122].

Esophageal cancer

Coptis decoction plays the inhibitory effect of oesophageal cancer through signaling pathways such as MAPK [123]. Kushen injection can inhibit tumor growth in esophageal cancer model rats by downregulating the PI3K/Akt signaling pathway [124]. Qigesan, Shashenmaidongtang, Tongyoutang and Buqiyunpitang can play important roles in inhibiting cell growth and leading to cell apoptosis, especially in promoting tumor cell apoptosis [125, 126]. Banxia Xiexin Tang affects the regulation point of the esophageal cancer cell cycle and promotes the apoptosis of tumor cells [127].

Pancreatic cancer

Xiao et al. utilized the bioinformatics database to deduce the possible treatment targets and associated biological pathways for the Prescription of detoxication of dryness-dampness in pancreatic cancer [128]. The use of Da Huang Mu Dan Tang in combination with exogenous somatostatin analogs may enhance the therapeutic effect of drugs on pancreatic cancer [129]. Zuojin Pills significantly inhibit cell cycle and proliferation and induce apoptosis [130]. Qingyihuaji formula can inhibit the growth and progression of pancreatic cancer via several mechanisms, including anti-inflammatory mechanisms and apoptosis induction [74]. Qingyihuaji formula can activate STAT1, inhibiting MAPK/ERK and PI3K/Akt/mTOR signaling pathways [131]. Qingyihuaji formulation counteracts gemcitabine-resistant human pancreatic cancer [132]. The primary active constituents in the Xiang-lian pill display anticancer activities by directly interacting with crucial targets in pancreatic cancer. The suppression of a selective MEK/ERK via prostaglandin-endoperoxide synthase 2 (PTGS2) by rutaecarpine is a crucial medicinal mechanism of the Xiang-lian pill [133].

Application of advanced technologies

Nevertheless, TCM faces several hurdles, including unpleasant odor, poor solubility, limited permeability, low bioavailability, rapid elimination, instability, short half-life, side effects, and high metabolic rates. In recent years, nano-targeted drug delivery systems have exhibited significant advantages in enhancing the specificity of TCM [134]. These systems improve TCM’s bioavailability, facilitate its distribution both in vivo and in vitro, enhance its pharmacokinetic properties, stabilize it, promote the dissolution of insoluble TCM components, protect it from degradation in vivo, increase its therapeutic efficacy, and reduce potential side effects [135]. Expanding this dialogue around nanotechnology in TCM can pave the way for innovative treatment strategies that bridge traditional practices with modern scientific advancements, ultimately improving patient outcomes in the management of digestive tract tumors.

Summary and outlook

With their many medicinal flavors and accurate syndrome differentiation, TCM compounds are crucial in Chinese medicine prescriptions. As patients present with complex conditions and diverse pathogenesis, single TCM herbs often fail to provide effective treatment. The advantages of TCM compounds lie in their ability to address more complex pathogenesis and diseases based on accurate syndrome differentiation. This approach has accumulated a wealth of clinical experience and greatly improved the efficacy of TCM prescriptions. Modern research on TCM compounds has revealed their multi-target, multi-level mechanisms of action, providing novel ideas and challenges.

However, TCM compounds still have significant challenges. One major issue is the lack of unified standards for drug preparation, and drug stability is often unclear. The preparation of TCM compounds must be based on efficacy and traditional medical experience. Nevertheless, technological advancements in preparation must also be made to ensure their safety and effectiveness in clinical practice. Besides, identifying and confirming various active ingredients and evaluating their stability within TCM compounds remains challenging. Progress in chromatography detection, serum detection technology, drug screening, and substance separation technology holds promise for enhancing the effectiveness of research on important TCM compounds.

Corresponding authors: Hang Song, School of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, China, E-mail: hangsong@ahtcm.edu.cn; and Xing-xing Huo, Experimental Center of Clinical Research, Scientific Research Department, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, China, E-mail: hxx0520@ahtcm.edu.cn

Yong-fu Zhu and Chang Liu contributed equally to this work.

Funding source: Horizontal scientific research Project

Award Identifier / Grant number: 2021HZ002

Award Identifier / Grant number: 2022HZ009

Funding source: Scientific Research project of Anhui Provincial Health Commission

Award Identifier / Grant number: AHWJ2022b053

Funding source: Scientific research project of Anhui University of Traditional Chinese Medicine

Award Identifier / Grant number: 2021yfylc44

Award Identifier / Grant number: 2022AH050415

Funding source: Project of Key Project of Anhui Provincial Department of Education

Award Identifier / Grant number: 2023AH050870

Award Identifier / Grant number: KJ2021A0557

Acknowledgments

We thank all authors who prepared, wrote, reviewed, and edited the entire manuscript.

Research ethics: Not applicable.
Informed consent: Not applicable.
Author contributions: Y-fZ, X-xH and HS conceived and designed the article; Y-fZ, CL and Y-dW retrieved documents; CL, JM, HZ designed illustrations, P-cZ, D-w Z, L-mX revised the paper; Y-fZ, CL, JX and HS wrote the paper. Every author has scrutinized and given their approval for the manuscript.
Use of Large Language Models, AI and Machine Learning Tools: None declared.
Conflict of interest: The authors state no conflict of interest.
Research funding: This work was supported by Project of Key Project of Anhui Provincial Department of Education (KJ2021A0557, 2023AH050870), Scientific Research project of Anhui Provincial Health Commission (AHWJ2022b053), Scientific research project of Anhui University of Traditional Chinese Medicine (2021yfylc44, 2022AH050508 and 2022AH050415) and Horizontal scientific research Project (2021HZ002 and 2022HZ009).
Data availability: Not applicable.

References

1. Xia, C, Dong, X, Li, H, Cao, M, Sun, D, He, S, et al.. Cancer statistics in China and United States, 2022: profiles, trends, and determinants. Chin Med J (Engl) 2022;135:584–90. https://doi.org/10.1097/cm9.0000000000002108.Search in Google Scholar PubMed PubMed Central

2. Cao, W, Chen, HD, Yu, YW, Li, N, Chen, WQ. Changing profiles of cancer burden worldwide and in China: a secondary analysis of the global cancer statistics 2020. Chin Med J (Engl) 2021;134:783–91. https://doi.org/10.1097/cm9.0000000000001474.Search in Google Scholar

3. Miao, K, Liu, W, Xu, J, Qian, Z, Zhang, Q. Harnessing the power of traditional Chinese medicine monomers and compound prescriptions to boost cancer immunotherapy. Front Immunol 2023;14:1277243. https://doi.org/10.3389/fimmu.2023.1277243.Search in Google Scholar PubMed PubMed Central

4. Chen, F, Li, J, Wang, H, Ba, Q. Anti-tumor effects of Chinese medicine compounds by regulating immune cells in microenvironment. Front Oncol 2021;11:746917. https://doi.org/10.3389/fonc.2021.746917.Search in Google Scholar PubMed PubMed Central

5. Zhang, X, Qiu, H, Li, C, Cai, P, Qi, F. The positive role of traditional Chinese medicine as an adjunctive therapy for cancer. Biosci Trends 2021;15:283–98. https://doi.org/10.5582/bst.2021.01318.Search in Google Scholar PubMed

6. Wang, H, Chen, ST, Ding, XJ, Kuai, L, Hua, L, Li, X, et al.. Efficacy and safety of Huzhang Granule, a compound Chinese herbal medicine, for acute gouty arthritis: a double-blind, randomized controlled trial. J Integr Med 2024;22:270–8. https://doi.org/10.1016/j.joim.2024.03.008.Search in Google Scholar PubMed

7. Yang, X, Feng, Y, Liu, Y, Ye, X, Ji, X, Sun, L, et al.. Fuzheng Jiedu Xiaoji formulation inhibits hepatocellular carcinoma progression in patients by targeting the AKT/CyclinD1/p21/p27 pathway. Phytomedicine 2021;87:153575. https://doi.org/10.1016/j.phymed.2021.153575.Search in Google Scholar PubMed

8. Cheng, L, Liu, W, Zhong, C, Ni, P, Ni, S, Wang, Q, et al.. Remodeling the homeostasis of pro- and anti-angiogenic factors by Shenmai injection to normalize tumor vasculature for enhanced cancer chemotherapy. J Ethnopharmacol 2021;270:113770. https://doi.org/10.1016/j.jep.2020.113770.Search in Google Scholar PubMed

9. Zhang, L, Liu, L, Zhao, L, Yuan, X, Wang, Y, Yang, J. Clinical efficacy of bushen Yiqi Fuzheng decoction combined with Sunitinib in the treatment of postoperative patients with renal cell carcinoma and its influence on their immune function. Arch Esp Urol 2023;76:538–47. https://doi.org/10.56434/j.arch.esp.urol.20237607.67.Search in Google Scholar PubMed

10. Zhou, H, Zhang, M, Cao, H, Du, X, Zhang, X, Wang, J, et al.. Research progress on the synergistic anti-tumor effect of natural anti-tumor components of Chinese herbal medicine combined with chemotherapy drugs. Pharmaceuticals 2023;16:1734. https://doi.org/10.3390/ph16121734.Search in Google Scholar PubMed PubMed Central

11. Gu, X, Hao, D, Xiao, P. Research progress of Chinese herbal medicine compounds and their bioactivities: fruitful 2020. Chin Herb Med 2022;14:171–86. https://doi.org/10.1016/j.chmed.2022.03.004.Search in Google Scholar PubMed PubMed Central

12. Lin, BW, Gong, CC, Song, HF, Cui, YY. Effects of anthocyanins on the prevention and treatment of cancer. Br J Pharmacol 2017;174:1226–43. https://doi.org/10.1111/bph.13627.Search in Google Scholar PubMed PubMed Central

13. Yu, M, Pan, Q, Li, W, Du, T, Huang, F, Wu, H, et al.. Isoliquiritigenin inhibits gastric cancer growth through suppressing GLUT4 mediated glucose uptake and inducing PDHK1/PGC-1α mediated energy metabolic collapse. Phytomedicine 2023;121:155045. https://doi.org/10.1016/j.phymed.2023.155045.Search in Google Scholar PubMed

14. Sheng, F, Yang, S, Li, M, Wang, J, Liu, L, Zhang, L. Research progress on the anti-cancer effects of Astragalus membranaceus saponins and their mechanisms of action. Molecules 2024;29:3388. https://doi.org/10.3390/molecules29143388.Search in Google Scholar PubMed PubMed Central

15. Banik, K, Khatoon, E, Harsha, C, Rana, V, Parama, D, Thakur, KK, et al.. Wogonin and its analogs for the prevention and treatment of cancer: a systematic review. Phytother Res 2022;36:1854–83. https://doi.org/10.1002/ptr.7386.Search in Google Scholar PubMed

16. Valdés-González, JA, Sánchez, M, Moratilla-Rivera, I, Iglesias, I, Gómez-Serranillos, MP. Immunomodulatory, anti-inflammatory, and anti-cancer properties of ginseng: a pharmacological update. Molecules 2023;28:3863. https://doi.org/10.3390/molecules28093863.Search in Google Scholar PubMed PubMed Central

17. Huang, Z, Gan, S, Zhuang, X, Chen, Y, Lu, L, Wang, Y, et al.. Artesunate inhibits the cell growth in colorectal cancer by promoting ROS-dependent cell senescence and autophagy. Cells 2022;11:2472. https://doi.org/10.3390/cells11162472.Search in Google Scholar PubMed PubMed Central

18. Dai, X, Zhang, X, Chen, W, Chen, Y, Zhang, Q, Mo, S, et al.. Dihydroartemisinin: a potential natural anticancer drug. Int J Biol Sci 2021;17:603–22. https://doi.org/10.7150/ijbs.50364.Search in Google Scholar PubMed PubMed Central

19. Wang, Y, Chen, M, Yu, H, Yuan, G, Luo, L, Xu, X, et al.. The role and mechanisms of action of natural compounds in the prevention and treatment of cancer and cancer metastasis. Front Biosci (Landmark Ed) 2022;27:192. https://doi.org/10.31083/j.fbl2706192.Search in Google Scholar PubMed

20. Wang, X, Xu, L, Lao, Y, Zhang, H, Xu, H. Natural products targeting EGFR signaling pathways as potential anticancer drugs. Curr Protein Pept Sci 2018;19:380–8. https://doi.org/10.2174/1389203718666170106104211.Search in Google Scholar PubMed

21. Kumar, A, Jaitak, V. Natural products as multidrug resistance modulators in cancer. Eur J Med Chem 2019;176:268–91. https://doi.org/10.1016/j.ejmech.2019.05.027.Search in Google Scholar PubMed

22. Howells, LM, Iwuji, COO, Irving, GRB, Barber, S, Walter, H, Sidat, Z, et al.. Curcumin combined with FOLFOX chemotherapy is safe and tolerable in patients with metastatic colorectal cancer in a randomized phase IIa trial. J Nutr 2019;149:1133–9. https://doi.org/10.1093/jn/nxz029.Search in Google Scholar PubMed PubMed Central

23. Lippert, E, Ruemmele, P, Obermeier, F, Goelder, S, Kunst, C, Rogler, G, et al.. Anthocyanins prevent colorectal cancer development in a mouse model. Digestion 2017;95:275–80. https://doi.org/10.1159/000475524.Search in Google Scholar PubMed

24. Zhao, H, Zhang, X, Chen, X, Li, Y, Ke, Z, Tang, T, et al.. Isoliquiritigenin, a flavonoid from licorice, blocks M2 macrophage polarization in colitis-associated tumorigenesis through downregulating PGE2 and IL-6. Toxicol Appl Pharmacol 2014;279:311–21. https://doi.org/10.1016/j.taap.2014.07.001.Search in Google Scholar PubMed

25. Zhang, Q, Liu, J, Liu, B, Xia, J, Chen, N, Chen, X, et al.. Dihydromyricetin promotes hepatocellular carcinoma regression via a p53 activation-dependent mechanism. Sci Rep 2014;4:4628. https://doi.org/10.1038/srep04628.Search in Google Scholar PubMed PubMed Central

26. Wang, F, Wang, L, Qu, C, Chen, L, Geng, Y, Cheng, C, et al.. Kaempferol induces ROS-dependent apoptosis in pancreatic cancer cells via TGM2-mediated Akt/mTOR signaling. BMC Cancer 2021;21:396. https://doi.org/10.1186/s12885-021-08158-z.Search in Google Scholar PubMed PubMed Central

27. Reyes-Farias, M, Carrasco-Pozo, C. The anti-cancer effect of quercetin: molecular implications in cancer metabolism. Int J Mol Sci 2019;20:3177. https://doi.org/10.3390/ijms20133177.Search in Google Scholar PubMed PubMed Central

28. Wang, Z, Ma, L, Su, M, Zhou, Y, Mao, K, Li, C, et al.. Baicalin induces cellular senescence in human colon cancer cells via upregulation of DEPP and the activation of Ras/Raf/MEK/ERK signaling. Cell Death Dis 2018;9:217. https://doi.org/10.1038/s41419-017-0223-0.Search in Google Scholar PubMed PubMed Central

29. Abdel-Hamid, NM, Zakaria, S, Nawaya, RA, Eldomany, RA, El-Shishtawy, MM. Daidzein and chicory extract arrest the cell cycle via inhibition of cyclin D/CDK4 and cyclin A/CDK2 gene expression in hepatocellular carcinoma. Recent Pat Anticancer Drug Discov 2022;18:187–99. https://doi.org/10.2174/1574892817666220321161318.Search in Google Scholar PubMed

30. Zhang, F, Yin, Y, Xu, W, Song, Y, Zhou, Z, Sun, X, et al.. Icariin inhibits gastric cancer cell growth by regulating the hsa_circ_0003159/miR-223-3p/NLRP3 signaling axis. Hum Exp Toxicol 2022;41:9603271221097363. https://doi.org/10.1177/09603271221097363.Search in Google Scholar PubMed

31. Lu, T, Zheng, C, Fan, Z. Cardamonin suppressed the migration, invasion, epithelial mesenchymal transition (EMT) and lung metastasis of colorectal cancer cells by down-regulating ADRB2 expression. Pharm Biol 2022;60:1011–21. https://doi.org/10.1080/13880209.2022.2069823.Search in Google Scholar PubMed PubMed Central

32. You, W, Di, A, Zhang, L, Zhao, G. Effects of wogonin on the growth and metastasis of colon cancer through the Hippo signaling pathway. Bioengineered 2022;13:2586–97. https://doi.org/10.1080/21655979.2021.2019173.Search in Google Scholar PubMed PubMed Central

33. Zhao, J, Li, L, Wang, Z, Li, L, He, M, Han, S, et al.. Luteolin attenuates cancer cell stemness in PTX-resistant oesophageal cancer cells through mediating SOX2 protein stability. Pharmacol Res 2021;174:105939. https://doi.org/10.1016/j.phrs.2021.105939.Search in Google Scholar PubMed

34. Gu, Q, Zhu, C, Wu, X, Peng, L, Huang, G, Hu, R. Wogonoside promotes apoptosis and ER stress in human gastric cancer cells by regulating the IRE1α pathway. Exp Ther Med 2021;21:411. https://doi.org/10.3892/etm.2021.9842.Search in Google Scholar PubMed PubMed Central

35. Arul, D, Subramanian, P. Naringenin (citrus flavonone) induces growth inhibition, cell cycle arrest and apoptosis in human hepatocellular carcinoma cells. Pathol Oncol Res 2013;19:763–70. https://doi.org/10.1007/s12253-013-9641-1.Search in Google Scholar PubMed

36. Cho, YR, Lee, JH, Kim, JH, Lee, SY, Yoo, S, Jung, MK, et al.. Matrine suppresses KRAS-driven pancreatic cancer growth by inhibiting autophagy-mediated energy metabolism. Mol Oncol 2018;12:1203–15. https://doi.org/10.1002/1878-0261.12324.Search in Google Scholar PubMed PubMed Central

37. Yi, B, Liu, D, He, M, Li, Q, Liu, T, Shao, J. Role of the ROS/AMPK signaling pathway in tetramethylpyrazine-induced apoptosis in gastric cancer cells. Oncol Lett 2013;6:583–9. https://doi.org/10.3892/ol.2013.1403.Search in Google Scholar PubMed PubMed Central

38. Du, YP, Peng, JS, Sun, A, Tang, ZH, Ling, WH, Zhu, HL. Assessment of the effect of betaine on p16 and c-myc DNA methylation and mRNA expression in a chemical induced rat liver cancer model. BMC Cancer 2009;9:261. https://doi.org/10.1186/1471-2407-9-261.Search in Google Scholar PubMed PubMed Central

39. Qu, M, Li, J, Yuan, L. Uncovering the action mechanism of homoharringtonine against colorectal cancer by using network pharmacology and experimental evaluation. Bioengineered 2021;12:12940–53. https://doi.org/10.1080/21655979.2021.2012626.Search in Google Scholar PubMed PubMed Central

40. Scheau, C, Badarau, IA, Caruntu, C, Mihai, GL, Didilescu, AC, Constantin, C, et al.. Capsaicin: effects on the pathogenesis of hepatocellular carcinoma. Molecules 2019;24:2350. https://doi.org/10.3390/molecules24132350.Search in Google Scholar PubMed PubMed Central

41. Feng, F, Pan, L, Wu, J, Li, L, Xu, H, Yang, L, et al.. Cepharanthine inhibits hepatocellular carcinoma cell growth and proliferation by regulating amino acid metabolism and suppresses tumorigenesis in vivo. Int J Biol Sci 2021;17:4340–52. https://doi.org/10.7150/ijbs.64675.Search in Google Scholar PubMed PubMed Central

42. Liao, F, Yang, Z, Lu, X, Guo, X, Dong, W. Sinomenine sensitizes gastric cancer cells to 5-fluorouracil in vitro and in vivo. Oncol Lett 2013;6:1604–10. https://doi.org/10.3892/ol.2013.1592.Search in Google Scholar PubMed PubMed Central

43. Liu, Y, Hua, W, Li, Y, Xian, X, Zhao, Z, Liu, C, et al.. Berberine suppresses colon cancer cell proliferation by inhibiting the SCAP/SREBP-1 signaling pathway-mediated lipogenesis. Biochem Pharmacol 2020;174:113776. https://doi.org/10.1016/j.bcp.2019.113776.Search in Google Scholar PubMed

44. Han, Z, Huang, H, Zhang, T. Downregulation of DBN1 is related to vincristine resistance in colon cancer cells. J Cancer Res Ther 2019;15:38–41. https://doi.org/10.4103/0973-1482.192766.Search in Google Scholar PubMed

45. Ma, Y, Yu, W, Shrivastava, A, Alemi, F, Lankachandra, K, Srivastava, RK, et al.. Sanguinarine inhibits pancreatic cancer stem cell characteristics by inducing oxidative stress and suppressing sonic hedgehog-Gli-Nanog pathway. Carcinogenesis 2017;38:1047–56. https://doi.org/10.1093/carcin/bgx070.Search in Google Scholar PubMed

46. Li, C, Tian, ZN, Cai, JP, Chen, KX, Zhang, B, Feng, MY, et al.. Panax ginseng polysaccharide induces apoptosis by targeting Twist/AKR1C2/NF-1 pathway in human gastric cancer. Carbohydr Polym 2014;102:103–9. https://doi.org/10.1016/j.carbpol.2013.11.016.Search in Google Scholar PubMed

47. Zhang, K, Zhou, X, Wang, J, Zhou, Y, Qi, W, Chen, H, et al.. Dendrobium officinale polysaccharide triggers mitochondrial disorder to induce colon cancer cell death via ROS-AMPK-autophagy pathway. Carbohydr Polym 2021;264:118018. https://doi.org/10.1016/j.carbpol.2021.118018.Search in Google Scholar PubMed

48. Miao, Y, Xiao, B, Jiang, Z, Guo, Y, Mao, F, Zhao, J, et al.. Growth inhibition and cell-cycle arrest of human gastric cancer cells by Lycium barbarum polysaccharide. Med Oncol 2010;27:785–90. https://doi.org/10.1007/s12032-009-9286-9.Search in Google Scholar PubMed

49. Wu, J, Yu, J, Wang, J, Zhang, C, Shang, K, Yao, X, et al.. Astragalus polysaccharide enhanced antitumor effects of Apatinib in gastric cancer AGS cells by inhibiting AKT signalling pathway. Biomed Pharmacother 2018;100:176–83. https://doi.org/10.1016/j.biopha.2018.01.140.Search in Google Scholar PubMed

50. Zhang, T, Shi, L, Li, Y, Mu, W, Zhang, H, Li, Y, et al.. Polysaccharides extracted from Rheum tanguticum ameliorate radiation-induced enteritis via activation of Nrf2/HO-1. J Radiat Res 2021;62:46–57. https://doi.org/10.1093/jrr/rraa093.Search in Google Scholar PubMed PubMed Central

51. Cheng, D, Zhang, X, Meng, M, Han, L, Li, C, Hou, L, et al.. Inhibitory effect on HT-29 colon cancer cells of a water-soluble polysaccharide obtained from highland barley. Int J Biol Macromol 2016;92:88–95. https://doi.org/10.1016/j.ijbiomac.2016.06.099.Search in Google Scholar PubMed

52. Liu, Z, Wu, X, Dai, K, Li, R, Zhang, J, Sheng, D, et al.. The new andrographolide derivative AGS-30 induces apoptosis in human colon cancer cells by activating a ROS-dependent JNK signalling pathway. Phytomedicine 2022;94:153824. https://doi.org/10.1016/j.phymed.2021.153824.Search in Google Scholar PubMed

53. Liu, Z, Li, L, Xue, B. Effect of ganoderic acid D on colon cancer Warburg effect: role of SIRT3/cyclophilin D. Eur J Pharmacol 2018;824:72–7. https://doi.org/10.1016/j.ejphar.2018.01.026.Search in Google Scholar PubMed

54. Liu, ML, Sun, D, Li, T, Chen, H. A systematic review of the immune-regulating and anticancer activities of pseudolaric acid B. Front Pharmacol 2017;8:394. https://doi.org/10.3389/fphar.2017.00394.Search in Google Scholar PubMed PubMed Central

55. Jiang, F, Zhou, JY, Zhang, D, Liu, MH, Chen, YG. Artesunate induces apoptosis and autophagy in HCT116 colon cancer cells, and autophagy inhibition enhances the artesunate-induced apoptosis. Int J Mol Med 2018;42:1295–304. https://doi.org/10.3892/ijmm.2018.3712.Search in Google Scholar PubMed PubMed Central

56. Liu, X, Du, P, Han, L, Zhang, A, Jiang, K, Zhang, Q. Effects of miR-200a and FH535 combined with taxol on proliferation and invasion of gastric cancer. Pathol Res Pract 2018;214:442–9. https://doi.org/10.1016/j.prp.2017.12.004.Search in Google Scholar PubMed

57. Ma, WL, Chang, N, Yu, Y, Su, YT, Chen, GY, Cheng, WC, et al.. Ursolic acid silences CYP19A1/aromatase to suppress gastric cancer growth. Cancer Med 2022;11:2824–35. https://doi.org/10.1002/cam4.4536.Search in Google Scholar PubMed PubMed Central

58. Yuan, W, Huang, J, Hou, S, Li, H, Bie, L, Chen, B, et al.. The antigastric cancer effect of triptolide is associated with H19/NF-κB/FLIP Axis. Front Pharmacol 2022;13:918588. https://doi.org/10.3389/fphar.2022.918588.Search in Google Scholar PubMed PubMed Central

59. Zhang, B, Han, H, Fu, S, Yang, P, Gu, Z, Zhou, Q, et al.. Dehydroeffusol inhibits gastric cancer cell growth and tumorigenicity by selectively inducing tumor-suppressive endoplasmic reticulum stress and a moderate apoptosis. Biochem Pharmacol 2016;104:8–18. https://doi.org/10.1016/j.bcp.2016.01.002.Search in Google Scholar PubMed

60. Giordano, A, Tommonaro, G. Curcumin and cancer. Nutrients 2019;11:2376. https://doi.org/10.3390/nu11102376.Search in Google Scholar PubMed PubMed Central

61. Chen, H, Huang, Y, Huang, J, Lin, L, Wei, G. Gigantol attenuates the proliferation of human liver cancer HepG2 cells through the PI3K/Akt/NF-κB signaling pathway. Oncol Rep 2017;37:865–70. https://doi.org/10.3892/or.2016.5299.Search in Google Scholar PubMed

62. Yang, R, Dong, H, Jia, S, Yang, Z. Resveratrol as a modulatory of apoptosis and autophagy in cancer therapy. Clin Transl Oncol 2022;24:1219–30. https://doi.org/10.1007/s12094-021-02770-y.Search in Google Scholar PubMed

63. Li, X, Li, X, Huang, N, Liu, R, Sun, R. A comprehensive review and perspectives on pharmacology and toxicology of saikosaponins. Phytomedicine 2018;50:73–87. https://doi.org/10.1016/j.phymed.2018.09.174.Search in Google Scholar PubMed PubMed Central

64. Min, L, Wang, H, Qi, H. Astragaloside IV inhibits the progression of liver cancer by modulating macrophage polarization through the TLR4/NF-κB/STAT3 signaling pathway. Am J Transl Res 2022;14:1551–66.Search in Google Scholar

65. Xu, J, Pan, Y, Liu, Y, Na, S, Zhou, H, Li, L, et al.. A review of anti-tumour effects of ginsenoside in gastrointestinal cancer. J Pharm Pharmacol 2021;73:1292–301. https://doi.org/10.1093/jpp/rgab048.Search in Google Scholar PubMed

66. Zhao, X, Xu, L, Zheng, L, Yin, L, Qi, Y, Han, X, et al.. Potent effects of dioscin against gastric cancer in vitro and in vivo. Phytomedicine 2016;23:274–82. https://doi.org/10.1016/j.phymed.2016.01.012. [Erratum in 2024;129:154932].Search in Google Scholar PubMed

67. Liu, HQ, Li, RH. Discussion on choking diaphragm in intergrating Chinese and western medicine. Zhejiang Zhong Yi Za Zhi 2019;54:631–2. https://doi.org/10.13633/j.cnki.zjtcm.2019.09.004. [article in Chinese].Search in Google Scholar

68. LoPiccolo, J, Blumenthal, GM, Bernstein, WB, Dennis, PA. Targeting the PI3K/Akt/mTOR pathway: effective combinations and clinical considerations. Drug Resist Updat 2008;11:32–50. https://doi.org/10.1016/j.drup.2007.11.003.Search in Google Scholar PubMed PubMed Central

69. Ciardiello, F, Tortora, G. EGFR antagonists in cancer treatment. N Engl J Med 2008;358:1160–74. https://doi.org/10.1056/nejmra0707704.Search in Google Scholar PubMed

70. Römer, L, Klein, C, Dehner, A, Kessler, H, Buchner, J. p53--a natural cancer killer: structural insights and therapeutic concepts. Angew Chem Int Ed Engl 2006;45:6440–60. https://doi.org/10.1002/anie.200600611.Search in Google Scholar PubMed

71. Clevers, H, Nusse, R. Wnt/β-catenin signaling and disease. Cell 2012;149:1192–205. https://doi.org/10.1016/j.cell.2012.05.012.Search in Google Scholar PubMed

72. Massagué, J. TGFbeta in cancer. Cell 2008;134:215–30. https://doi.org/10.1016/j.cell.2008.07.001.Search in Google Scholar PubMed PubMed Central

73. DiDonato, JA, Mercurio, F, Karin, M. NF-κB and the link between inflammation and cancer. Immunol Rev 2012;246:379–400. https://doi.org/10.1111/j.1600-065x.2012.01099.x.Search in Google Scholar PubMed

74. Fan, JH, Xu, MM, Zhou, LM, Gui, ZW, Huang, L, Li, XG, et al.. Integrating network pharmacology deciphers the action mechanism of Zuojin capsule in suppressing colorectal cancer. Phytomedicine 2022;96:153881. https://doi.org/10.1016/j.phymed.2021.153881.Search in Google Scholar PubMed

75. Huang, S, Zhang, Z, Li, W, Kong, F, Yi, P, Huang, J, et al.. Network pharmacology-based prediction and verification of the active ingredients and potential targets of Zuojinwan for treating colorectal cancer. Drug Des Devel Ther 2020;14:2725–40. https://doi.org/10.2147/dddt.s250991.Search in Google Scholar

76. Zhuang, Q, Hong, F, Shen, A, Zheng, L, Zeng, J, Lin, W, et al.. Pien Tze Huang inhibits tumor cell proliferation and promotes apoptosis via suppressing the STAT3 pathway in a colorectal cancer mouse model. Int J Oncol 2012;40:1569–74. https://doi.org/10.3892/ijo.2012.1326.Search in Google Scholar PubMed

77. Tang, RZ, Li, ZZ, Hu, D, Kanwal, F, Yuan, CB, Mustaqeem, M, et al.. Sanjie Yiliu formula inhibits colorectal cancer growth by suppression of proliferation and induction of apoptosis. ACS Omega 2021;6:7761–70. https://doi.org/10.1021/acsomega.0c05565.Search in Google Scholar PubMed PubMed Central

78. Yang, H, Liu, JX, Shang, HX, Lin, S, Zhao, JY, Lin, JM. Qingjie Fuzheng granules inhibit colorectal cancer cell growth by the PI3K/AKT and ERK pathways. World J Gastrointest Oncol 2019;11:377–92. https://doi.org/10.4251/wjgo.v11.i5.377.Search in Google Scholar PubMed PubMed Central

79. Zhu, XQ, Yang, H, Lin, MH, Shang, HX, Peng, J, Chen, WJ, et al.. Qingjie Fuzheng Granules regulates cancer cell proliferation, apoptosis and tumor angiogenesis in colorectal cancer xenograft mice via Sonic Hedgehog pathway. J Gastrointest Oncol 2020;11:1123–34. https://doi.org/10.21037/jgo-20-213.Search in Google Scholar PubMed PubMed Central

80. Huang, B, Lu, Y, Gui, M, Guan, J, Lin, M, Zhao, J, et al.. Qingjie Fuzheng Granule suppresses lymphangiogenesis in colorectal cancer via the VEGF-C/VEGFR-3 dependent PI3K/AKT pathway. Biomed Pharmacother 2021;137:111331. https://doi.org/10.1016/j.biopha.2021.111331.Search in Google Scholar PubMed

81. Zhu, YF, Xu, J, Wu, J, Ma, J, Zhang, DW, Xia, LM, et al.. Compound shougong powder inhibits the malignant phenotype of hepatocellular carcinoma cells by targeting the DNA damage repair pathway. J Pharm Pharmacol 2023;75:703–11. https://doi.org/10.1093/jpp/rgad026.Search in Google Scholar PubMed

82. Li, L, Wang, K, Liu, Z, Lü, Y, Wang, C, Yi, X, et al.. Compound Kushen injection inhibits EMT of gastric cancer cells via the PI3K/AKT pathway. World J Surg Oncol 2022;20:161. https://doi.org/10.1186/s12957-022-02609-y.Search in Google Scholar PubMed PubMed Central

83. Liu, X, Ji, Q, Deng, W, Chai, N, Feng, Y, Zhou, L, et al.. JianPi JieDu Recipe inhibits epithelial-to-mesenchymal transition in colorectal cancer through TGF-β/Smad mediated snail/E-cadherin expression. BioMed Res Int 2017;2017:2613198–11. https://doi.org/10.1155/2017/2613198.Search in Google Scholar PubMed PubMed Central

84. Lin, W, Zhuang, Q, Zheng, L, Cao, Z, Shen, A, Li, Q, et al.. Pien Tze Huang inhibits liver metastasis by targeting TGF-β signaling in an orthotopic model of colorectal cancer. Oncol Rep 2015;33:1922–8. https://doi.org/10.3892/or.2015.3784.Search in Google Scholar PubMed

85. Shen, A, Lin, W, Chen, Y, Liu, L, Chen, H, Zhuang, Q, et al.. Pien Tze Huang inhibits metastasis of human colorectal carcinoma cells via modulation of TGF-β1/ZEB/miR-200 signaling network. Int J Oncol 2015;46:685–90. https://doi.org/10.3892/ijo.2014.2772.Search in Google Scholar PubMed

86. Song, SJ, Liu, X, Ji, Q, Sun, DZ, Xiu, LJ, Xu, JY, et al.. Ziyin Huatan Recipe, a Chinese herbal compound, inhibits migration and invasion of gastric cancer by upregulating RUNX3 expression. J Integr Med 2022;20:355–64. https://doi.org/10.1016/j.joim.2022.02.006.Search in Google Scholar PubMed

87. Tao, L, Gu, Y, Zheng, J, Yang, J, Zhu, Y. Weichang’an suppressed migration and invasion of HCT116 cells by inhibiting Wnt/β-catenin pathway while upregulating ARHGAP25. Biotechnol Appl Biochem 2019;66:787–93. https://doi.org/10.1002/bab.1784.Search in Google Scholar PubMed

88. Yang, PW, Xu, PL, Cheng, CS, Jiao, JY, Wu, Y, Dong, S, et al.. Integrating network pharmacology and experimental models to investigate the efficacy of QYHJ on pancreatic cancer. J Ethnopharmacol 2022;297:115516. https://doi.org/10.1016/j.jep.2022.115516.Search in Google Scholar PubMed

89. Yang, Y, Sun, M, Yao, W, Wang, F, Li, X, Wang, W, et al.. Compound kushen injection relieves tumor-associated macrophage-mediated immunosuppression through TNFR1 and sensitizes hepatocellular carcinoma to sorafenib. J Immunother Cancer 2020;8:e000317. https://doi.org/10.1136/jitc-2019-000317.Search in Google Scholar PubMed PubMed Central

90. Chen, TT, Du, SL, Wang, SJ, Wu, L, Yin, L. Dahuang Zhechong pills inhibit liver cancer growth in a mouse model by reversing Treg/Th1 balance. Chin J Nat Med 2022;20:102–10. https://doi.org/10.1016/s1875-5364(22)60160-2.Search in Google Scholar

91. Yuan, M, Zou, X, Liu, S, Xu, X, Wang, H, Zhu, M, et al.. Modified Jian-pi-yang-zheng decoction inhibits gastric cancer progression via the macrophage immune checkpoint PI3Kγ. Biomed Pharmacother 2020;129:110440. https://doi.org/10.1016/j.biopha.2020.110440.Search in Google Scholar PubMed

92. Wu, J, Zhang, XX, Zou, X, Wang, M, Wang, HX, Wang, YH, et al.. The effect of Jianpi Yangzheng Xiaozheng Decoction and its components on gastric cancer. J Ethnopharmacol 2019;235:56–64. https://doi.org/10.1016/j.jep.2019.02.003.Search in Google Scholar PubMed

93. Zhang, Y, Chai, N, Wei, Z, Li, Z, Zhang, L, Zhang, M, et al.. YYFZBJS inhibits colorectal tumorigenesis by enhancing Tregs-induced immunosuppression through HIF-1α mediated hypoxia in vivo and in vitro. Phytomedicine 2022;98:153917. https://doi.org/10.1016/j.phymed.2021.153917.Search in Google Scholar PubMed

94. Shi, J, Lu, Y, Wei, P. Xiaotan Sanjie decoction inhibits angiogenesis in gastric cancer through Interleukin-8-linked regulation of the vascular endothelial growth factor pathway. J Ethnopharmacol 2016;189:230–7. https://doi.org/10.1016/j.jep.2016.05.043.Search in Google Scholar PubMed

95. Yan, B, Liu, L, Zhao, Y, Xiu, LJ, Sun, DZ, Liu, X, et al.. Xiaotan Sanjie decoction attenuates tumor angiogenesis by manipulating Notch-1-regulated proliferation of gastric cancer stem-like cells. World J Gastroenterol 2014;20:13105–18. https://doi.org/10.3748/wjg.v20.i36.13105.Search in Google Scholar PubMed PubMed Central

96. Lin, X, Xu, L, Tan, H, Zhang, X, Shao, H, Yao, L, et al.. The potential effects and mechanisms of Gegen Qinlian Decoction in oxaliplatin-resistant colorectal cancer based on network pharmacology. Heliyon 2022;8:e11305. https://doi.org/10.1016/j.heliyon.2022.e11305.Search in Google Scholar PubMed PubMed Central

97. Shao, L, Zhu, L, Su, R, Yang, C, Gao, X, Xu, Y, et al.. Baicalin enhances the chemotherapy sensitivity of oxaliplatin-resistant gastric cancer cells by activating p53-mediated ferroptosis. Sci Rep 2024;14:10745. https://doi.org/10.1038/s41598-024-60920-y.Search in Google Scholar PubMed PubMed Central

98. Lin, X, Xu, L, Gu, M, Shao, H, Yao, L, Huang, X. Gegen Qinlian Decoction reverses oxaliplatin resistance in colorectal cancer by inhibiting YTHDF1-regulated m6A modification of GLS1. Phytomedicine 2024;133:155906. https://doi.org/10.1016/j.phymed.2024.155906.Search in Google Scholar PubMed

99. Ou, QL, Cheng, L, Chang, YL, Liu, JH, Zhang, SF. Jianpi Jiedu decoction reverses 5-fluorouracil resistance in colorectal cancer by suppressing the xCT/GSH/GPX4 axis to induce ferroptosis. Heliyon 2024;10:e27082. https://doi.org/10.1016/j.heliyon.2024.e27082.Search in Google Scholar PubMed PubMed Central

100. Shalapour, S, Karin, M. Cruel to be kind: epithelial, microbial, and immune cell interactions in gastrointestinal cancers. Annu Rev Immunol 2020;38:649–71. https://doi.org/10.1146/annurev-immunol-082019-081656.Search in Google Scholar PubMed PubMed Central

101. Bray, F, Laversanne, M, Sung, H, Ferlay, J, Siegel, RL, Soerjomataram, I, et al.. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2024;74:229–63. https://doi.org/10.3322/caac.21834.Search in Google Scholar PubMed

102. Ma, NX, Sun, W, Wu, J, Liu, SL, Weng, L, Liu, YQ, et al.. Compound Wumei powder inhibits the invasion and metastasis of gastric cancer via Cox-2/PGE2-PI3K/AKT/GSK3beta/beta-Catenin signaling pathway. Evid Based Complement Alternat Med 2017;2017:3039450. https://doi.org/10.1155/2017/3039450.Search in Google Scholar PubMed PubMed Central

103. Wang, YZ, Wang, JL, Zhu, XJ. Effect of compound lizard powder Gel on rats with precancerous lesions of gastric cancer based on PI3K/Akt/mTOR signaling pathway. Zhongyi Xuebao 2021;36:2154–8. https://doi.org/10.16368/j.issn.1674-8999.2021.10.451. [article in Chinese].Search in Google Scholar

104. Jie, Y, Yin, KF, Yan, PS, Ye, L. Mechanism of apoptosis and related apoptosis genes Bax and Bcl-2 induced by Fupi Hualiu decoction in MFC gastric cancer mice. Shaanxi Zhong Yi 2019;40:550–2+90. https://doi.org/10.3969/j.issn.1000-7369.2019.05.002. [article in Chinese].Search in Google Scholar

105. Tian, YH, Zhao, JX, Zhou, C, Qiu, XW, Huang, JC, Jin, XH. Study on mechanism of Banxia Xiexin decoction treating gastric cancer based on network pharmacology. Liaoning Zhong Yi Za Zhi 2021;48:147–52+221–2. https://doi.org/10.13192/j.issn.1000-1719.2021.01.042. [article in Chinese].Search in Google Scholar

106. Lu, Q, Guan, JH, Zeng, JW, Lin, MH, Weygant, N, Cao, ZY. Study on the biological mechanism of Jiedu Xiaozheng Yin in regulating glucose energy metabolism and lnhibiting hepatocellular carcinoma cell proliferation through HIF-1/miR-210. Fujian Zhong Yi Yao 2022;53:34–41. https://doi.org/10.3969/j.issn.1000-338X.2022.11.010. [article in Chinese].Search in Google Scholar

107. Qiao, X, Xu, SH, Wang, YW, Feng, B, Peng, PK, Shen, KK. Da Chaihutang inhibits hepatocellular carcinoma by regulating p38 MAPK/IL-6/STAT3 signaling pathway. Chin J Exp Tradit Med Form 2022;28:19–31. https://doi.org/10.13422/j.cnki.syfjx.20221026. [article in Chinese].Search in Google Scholar

108. Sun, J, Han, T, Yang, T, Chen, Y, Huang, J. Interpreting the molecular mechanisms of Yinchenhao decoction on hepatocellular carcinoma through absorbed components based on network pharmacology. BioMed Res Int 2021;2021:6616908–22. https://doi.org/10.1155/2021/6616908.Search in Google Scholar PubMed PubMed Central

109. Li, MS, Zhang, GX, Chen, H, Qin, W, Wei, YY. Mechanism of modified Yinchenhao decoction inhibiting subcutaneous transplantation tumor of human hepatocarcinoma in nude mice. Zhongyi Xuebao 2020;35:1059–64. https://doi.org/10.16368/j.issn.1674-8999.2020.05.238. [article in Chinese].Search in Google Scholar

110. Cao, SL, Fan, LF, Wang, N, Ma, DQ. Effect of Fuzheng Yiliu decoction on nude mice model of human hepatoma cell Hu-7 xenograft. Zhong Yi Yao Dao Bao 2018;24:66–8+71. https://doi.org/10.13862/j.cnki.cn43-1446/r.2018.24.021. [article in Chinese].Search in Google Scholar

111. Xiu, YH, Zi, LH, Yong, HX, Zhi, GW, Xin, YH, Qi, Z, et al.. Experimental research on apoptosis of hepatocellular carcinoma induced by Chinese herbal compound Songyou Yin. Zhonghua Zhong Yi Yao Xue Kan 2014;32:249–51. https://doi.org/10.13193/j.issn.1673-7717.2014.02.007. [article in Chinese].Search in Google Scholar

112. Liu, Z, Tian, XF, Gao, WH, Tan, XN, Jian, HY, Li, KX, et al.. Molecular mechanisms of Gupi Xiaoji decoction inducing apoptosis of human hepatoma HepG2 cells. Zhongguo Ying Yong Sheng Li Xue Za Zhi 2022;38:247–51+57. https://doi.org/10.12047/j.cjap.6292.2022.049. [article in Chinese].Search in Google Scholar PubMed

113. Chun, HN, Xin, QT, Zhuang, YZ. Study of Qiye Baogan decoction on proliferation and apoptosis of hepatocellular carcinoma cells. Zhongguo Zhong Yi Ji Chu Yi Xue Za Zhi 2016;22:59–61+92. https://doi.org/10.19945/j.cnki.issn.1006-3250.2016.01.025. [article in Chinese].Search in Google Scholar

114. Xia, Y, Li, T, Sun, MY. Experimental study on intervention of traditional Chinese medicine compound Cerebiogen capsule for intervention of colon cancer angiogenesis via VEGF/VEGFR2 signaling pathway. Zhongguo Mian Yi Xue Za Zhi 2020;36:1318–23. https://doi.org/10.3969/j.issn.1000-484X.2020.11.008. [article in Chinese].Search in Google Scholar

115. An, YK, Yin, Q, Zhang, SX, Han, HT, Wu, F, Liu, XB, et al.. Effect on apoptosis of human colon cancer SW480 cells by traditional Chinese medicine compound of Zangduqing. Chin J Exp Tradit Med Form 2015;21:155–8. https://doi.org/10.13422/j.cnki.syfjx.2015070155. [article in Chinese].Search in Google Scholar

116. Huang, XW, Wang, SS, Zheng, JL, Chen, L, Peng, X, Chen, JF, et al.. Effects of Tenglong Buzhong decoction on immune function of tumor-bearing mice with colorectal cancer. Hebei Zhong Yi 2022;44:1512–4+8. https://doi.org/10.3969/j.issn.1002-2619.2022.09.023. [article in Chinese].Search in Google Scholar

117. Chen, LY, Zhu, YY, Wang, XX, Shi, XL. Si Junzitang regulates NKG2A expression to improve anti-colon cancer function of NK cells. Chin J Exp Med Formul 2022;28:28–34. https://doi.org/10.13422/j.cnki.syfjx.20220926. [article in Chinese].Search in Google Scholar

118. Liang, ZC, Wen, L, Chen, HX, Zhao, X, Wang, X. Mechanism of action of Dahuang Mudan decoction in treatment of colorectal cancer based on network pharmacology-molecular docking. Hunan Zhong Yi Za Zhi 2021;37:177–82+89. https://doi.org/10.16808/j.cnki.issn1003-7705.2021.10.057. [article in Chinese].Search in Google Scholar

119. Bao, YJ, Gao, F, Wang, DY, Chen, JB, Wu, HL, Jia, LL. Regulating effect of Xiangsha Liujunzi decoction on colon cancer bearing nude mice. Zhong Yi Xue Bao 2021;36:2159–65. https://doi.org/10.16368/j.issn.1674-8999.2021.10.452. [article in Chinese].Search in Google Scholar

120. Wang, J, Bai, X, Zhou, J, Zhang, XD, Bao, FH. Effect of oral administration of Fuzheng Shengbai Decoction on white blood cell counts, miR-125b and miR-124 of colorectal cancer patients after chemotherapy. Zhong Hua Yi Yuan Gan Ran Xue Za Zhi 2021;31:1481–5. https://doi.org/10.11816/cn.ni.2021-203066. [article in Chinese.Search in Google Scholar

121. Li, LM. Inhibitory effect of Banxia Xiexin decoction-containing serum on proliferation of colon cancer cells and growth of human colon cancer Xenografts in nude mice. Liaoning Zhong Yi Yao Da Xue Xue Bao 2019;21:37–40. https://doi.org/10.13194/j.issn.1673-842x.2019.12.009. [article in Chinese].Search in Google Scholar

122. Zhang, XY, Zhong, R, Cui, HJ, Zhao, XY, Li, SY. Inhibitory effects of Modified Sijunzi Decoction on transplanted tumor of CT26 colorectal cancer in mice and influence on protein expressions of tumor-associated macrophages CD68 and CD206. Shanghai Zhong Yi Yao Da Xue Xue Bao 2019;33:61–5. https://doi.org/10.16306/j.1008-861x.2019.02.014. [article in Chinese].Search in Google Scholar

123. Zhou, MY, Wang, W, Liu, L, Yang, ZL, Tan, YH. Study on the mechanism of compound coptis decoction in the treatment of esophageal cancer. Xian Dai Yi Yao Wei Sheng 2022;38:2735–9. https://doi.org/10.3969/j.issn.1009-5519.2022.16.008. [article in Chinese].Search in Google Scholar

124. Yue, XZ, Pin, L, Bing, QL, Jian, C. Exploring the protection mechanism of Compound Kushen injection to esophageal cancer model rats based on PI3K/Akt pathway. Zhong Yao Cai 2021;44:196–9. https://doi.org/10.13863/j.issn1001-4454.2021.01.037. [article in Chinese].Search in Google Scholar

125. Lv, CT, Si, FC, Chen, YL. Effects of Qige powder, Shashen Maidong decoction and Tongyou decoction on Caspase-3-mediated apoptosis signal transduction in human esophageal carcinoma cell EC9706. Liaoning Zhong Yi Za Zhi 2016;43:1455–8+1. https://doi.org/10.13192/j.issn.1000-1719.2016.07.038. [article in Chinese].Search in Google Scholar

126. Si, FC. Effects of Qigesan, Shashenmaidongtang, Tongyoutang and Buqiyunpitang on hEGF-stimulated proliferation of human esophageal carcinoma EC9706 cells. Shi Jie Hua Ren Xiao Hua Za Zhi 2010;18:2956–65. https://doi.org/10.3969/j.issn.1009-3079.2008.28.002. [article in Chinese].Search in Google Scholar

127. Cui, SS, Shao, L, Gao, XL, Wu, YS. Effect of Banxia Xiexin Tang on cell cycle, apoptosis and STAT3 protein expression of esophageal carcinoma Eca9706 cells. Chin J Exp Med Formul 2016;22:142–5. https://doi.org/10.13422/j.cnki.syfjx.2016040142. [article in Chinese].Search in Google Scholar

128. Wang, XL, Lei, YY, Li, JK, Gao, SS, Cai, DF. Effect of the compound prescription of detoxication of dryness-dampness on pancreatic cancer based on tumor-bearing mouse model and bioinformatic. Fudan Univ J Med Sci 2022;49:916–23. https://doi.org/10.3969/j.issn.1672-8467.2022.06.011. [article in Chinese].Search in Google Scholar

129. Wang, YJ, Zhang, M, Meng, B, You, GH. Treatment effect of Da Huang Mu Dan Tang in rats with pancreatic carcinoma and protective effects on liver and kindey function. J Jilin Univ - Med Ed 2017;43:1069–73+11. https://doi.org/10.13481/j.1671-587x.20170601. [article in Chinese].Search in Google Scholar

130. Wang, K, Miao, X, Kong, F, Huang, S, Mo, J, Jin, C, et al.. Integrating network pharmacology and experimental verification to explore the mechanism of effect of Zuojin pills in pancreatic cancer treatment. Drug Des Devel Ther 2021;15:3749–64. https://doi.org/10.2147/dddt.s323360.Search in Google Scholar PubMed PubMed Central

131. Qian, X, Bi, QY, Wang, ZN, Han, F, Liu, LM, Song, LB, et al.. Qingyihuaji Formula promotes apoptosis and autophagy through inhibition of MAPK/ERK and PI3K/Akt/mTOR signaling pathway on pancreatic cancer in vivo and in vitro. J Ethnopharmacol 2023;307:116198. https://doi.org/10.1016/j.jep.2023.116198.Search in Google Scholar PubMed

132. Chen, P, Wang, M, Wang, C. Qingyihuaji formula reverses gemcitabine resistant human pancreatic cancer through regulate lncRNA AB209630/miR-373/EphB2-NANOG signals. Biosci Rep 2019;39:BSR20190610. https://doi.org/10.1042/bsr20190610.Search in Google Scholar

133. Jiao, J, Cheng, CS, Xu, P, Yang, P, Zhang, K, Jing, Y, et al.. Mechanisms of pancreatic tumor suppression mediated by Xiang-lian pill: an integrated in silico exploration and experimental validation. J Ethnopharmacol 2022;298:115586. https://doi.org/10.1016/j.jep.2022.115586.Search in Google Scholar PubMed

134. Zheng, Y, Wang, Y, Xia, M, Gao, Y, Zhang, L, Song, Y, et al.. The combination of nanotechnology and traditional Chinese medicine (TCM) inspires the modernization of TCM: review on nanotechnology in TCM-based drug delivery systems. Drug Deliv Transl Res 2022;12:1306–25. https://doi.org/10.1007/s13346-021-01029-x.Search in Google Scholar PubMed

135. Ke, G, Zhang, J, Gao, W, Chen, J, Liu, L, Wang, S, et al.. Application of advanced technology in traditional Chinese medicine for cancer therapy. Front Pharmacol 2022;13:1038063. https://doi.org/10.3389/fphar.2022.1038063.Search in Google Scholar PubMed PubMed Central

Received: 2024-07-03

Accepted: 2024-10-13

Published Online: 2024-11-13

This work is licensed under the Creative Commons Attribution 4.0 International License.

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https://doi.org/10.1515/oncologie-2024-0340

Keywords for this article

Chinese medicine; Chinese medicine compound; natural products; digestive tract; anti-tumor; mechanism

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