Startseite The differential role of resistin on invasive liver cancer cells
Artikel
Lizenziert
Nicht lizenziert Erfordert eine Authentifizierung

The differential role of resistin on invasive liver cancer cells

  • Candace Miethe , Kelsie Raign , Megan Zamora und Ramona Salcedo Price EMAIL logo
Veröffentlicht/Copyright: 3. März 2023
Veröffentlichen auch Sie bei De Gruyter Brill

Abstract

Objectives

To determine whether inhibition of kinase signaling will suppress resistin-induced liver cancer progression. Resistin is located in monocytes and macrophages of adipose tissue. This adipocytokine is an important link between obesity, inflammation, insulin resistance, and cancer risk. Pathways that resistin is known to be involved include but are not limited to mitogen-activated protein kinases (MAPKs) and extracellular signal-regulated kinases (ERK). The ERK pathway promotes cellular proliferation, migration, survival of cancer cells, and tumor progression. The Akt pathway is known to be up-regulated in many cancers including liver cancer.

Methods

Using an in vitro model, HepG2 and SNU-449 liver cancer cells were exposed to resistin ± ERK, Akt, or both inhibitors. The following physiological parameters were assessed: cellular proliferation, ROS, lipogenesis, invasion, MMP, and lactate dehydrogenase activity.

Results

The inhibition of kinase signaling suppressed resistin-induced invasion and lactate dehydrogenase in both cell lines. In addition, in SNU-449 cells, resistin increased proliferation, ROS, and MMP-9 activity. Inhibition of PI3K and ERK decreased phosphorylated Akt and ERK, and pyruvate dehydrogenase.

Conclusions

In this study, we describe the effect of Akt and ERK inhibitors to determine if inhibition suppresses resistin-induced liver cancer progression. Resistin promotes cellular proliferation, ROS, MMP, invasion and LDH activity in SNU-449 liver cancer cells which is differentially mediated by Akt and ERK signaling pathways.


Corresponding author: Ramona Salcedo Price, Nutrition and Foods, Texas State University, San Marcos, 601 University Dr. San Marcos, TX 78666, USA, Phone: +1 512 245 6202, Fax: +1 512 245 3829, E-mail:

  1. Research funding: This study was funded internally from Texas State University.

  2. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  3. Competing interests: Authors state no conflict of interest.

  4. Informed consent: Not applicable.

  5. Ethical approval: The conducted research does not include the use of human participants or animals.

References

1. The American Cancer Society. Available from: https://www.cancer.org/cancer/liver-cancer/about/what-is-key-statistics.html [Accessed 14 Feb 2021].Suche in Google Scholar

2. Hanahan, D, Weinberg, R. Hallmarks of cancer: the next generation. Cell 2011;144:646–74. https://doi.org/10.1016/j.cell.2011.02.013.Suche in Google Scholar PubMed

3. CDC. Adult obesity facts. Available from: https://www.cdc.gov/nchs/products/databriefs/db360.htm [Accessed 14 Feb 2021].Suche in Google Scholar

4. Miethe, C, Nix, H, Martin, R, Hernandez, AR, Price, RS. Silibinin reduces the impact of obesity on invasive liver cancer. J Nutr Cancer 2017;69:1272–80. https://doi.org/10.1080/01635581.2017.1367935.Suche in Google Scholar PubMed

5. Luo, Z, Zhang, Y, Li, F, He, J, Ding, H, Yan, L, et al.. Resistin induces insulin resistance by both AMPK-dependent and AMPK-independent mechanisms in HepG2 cells. Endocrine 2009;36:60–9. https://doi.org/10.1007/s12020-009-9198-7.Suche in Google Scholar PubMed

6. Gholinejad, Z, Kheiripour, N, Nourbakhsh, M, Ilbeigi, D, Behroozfar, K, Hesari, Z, et al.. Extracellular NAMPT/visfatin induces proliferation through ERK1/2 and AKT and inhibits apoptosis in breast cancer cells. Pept Int J 2017;92:9–15. https://doi.org/10.1016/j.peptides.2017.04.007.Suche in Google Scholar PubMed

7. Wu, X, Yang, L. Signaling pathways in liver cancer. Liver Tumors 2012;10:37–58.10.5772/31381Suche in Google Scholar

8. Lee, S, Lee, HC, Kwon, YW, Lee, SE, Cho, Y, Kim, J, et al.. Adenylyl cyclase-associated protein 1 is a receptor for human resistin and mediates inflammatory actions of human monocytes. Cell Metabol 2014;19:484–97. https://doi.org/10.1016/j.cmet.2014.01.013.Suche in Google Scholar PubMed PubMed Central

9. Feitelson, M, Arzumanyan, A, Kulathinal, R, Blain, SW, Holcombe, RF, Mahajna, J, et al.. Sustained proliferation in cancer: mechanisms and noel therapeutic targets. Semin Cancer Biol 2015;35:S25–54. https://doi.org/10.1016/j.semcancer.2015.02.006.Suche in Google Scholar PubMed PubMed Central

10. Wu, R, Duan, L, Cui, F, Cao, J, Xiang, Y, Tang, Y, et al.. S100A9 promotes human hepatocellular carcinoma cell growth and invasion through RAGE-mediated ERK1/2 and p38 MAPK pathways. Exp Cell Res 2015;334:228–38. https://doi.org/10.1016/j.yexcr.2015.04.008.Suche in Google Scholar PubMed

11. Guo, Y, Ma, J, Wu, L, Wang, Q, Li, X, Li, X, et al.. Hyperthermia-induced NDRG2 upregulation inhibits the invasion of human hepatocellular carcinoma via suppressing ERK1/2 signaling pathway. PLoS One 2013;8:e61079. https://doi.org/10.1371/journal.pone.0061079.Suche in Google Scholar PubMed PubMed Central

12. Azuma, K, Katsukawa, F, Oguchi, S, Murata, M, Yamazaki, H, Shimada, A, et al.. Correlation between serum resistin level and adiposity in obese individuals. Obes Res 2003;11:997–1001. https://doi.org/10.1038/oby.2003.137.Suche in Google Scholar PubMed

13. Nieva-Vazquez, A, Pérez-Fuentes, R, Torres-Rasgado, E, Lopez-Lopez, JG, Romero, JR. Serum resistin levels are associated with adiposity and insulin sensitivity in obese hispanic subjects. Metab Syndr Relat Disord 2014;12:143–8. https://doi.org/10.1089/met.2013.0118.Suche in Google Scholar PubMed PubMed Central

14. Akhtar, A, Saeed, M, Shakoor, Q. Relationship of serum resistin and lipid profile in type 2 diabetics. Pak J Physiol 2017;13:3–5.Suche in Google Scholar

15. Tolosa, L, Donato, MT, Gómez-Lechón, MJ. General cytotoxicity assessment by means of the MTT assay. In: Protocols in in vitro hepatocyte research. New York, NY: Humana Press; 2015:333–48 pp.10.1007/978-1-4939-2074-7_26Suche in Google Scholar PubMed

16. Corning. Corning BioCoat matrigel invasion chamber. Available from: https://www.corning.com/media/jp/cls/documents/jp-literature/applicationnotej/Matrigel_Invasion_Chamber_6-Experimental_Procedure-2_6-Other-5_Protocol_6-Reference_EN.pdf [Accessed 7 Feb 2018].Suche in Google Scholar

17. ThermoFisher Scientific. MMP9 human ELISA kit. Available from: https://www.thermofisher.com/order/catalog/product/BMS2016-2 [Accessed 12 Feb 2018].Suche in Google Scholar

18. Sigma-Aldrich. Lactate dehydrogenase activity assay kit. Available from: https://www.sigmaaldrich.com/content/dam/sigma-aldrich/docs/Sigma/Bulletin/1/mak066bul.pdf [Accessed 30 Mar 2018].Suche in Google Scholar

19. ThermoFisher, Scientific. BCA protein assay kit. Available from: https://www.thermofisher.com/order/catalog/product/23225 [Accessed 12 Feb 2018].Suche in Google Scholar

20. Mounier, C, Bouraoui, L, Rassart, E. Lipogenesis in cancer progression. Int J Oncol 2014;45:485–92. https://doi.org/10.3892/ijo.2014.2441.Suche in Google Scholar PubMed

21. Liou, G, Storz, P. Reactive oxygen species in cancer. Free Radic Res 2010;44:479–96. https://doi.org/10.3109/10715761003667554.Suche in Google Scholar PubMed PubMed Central

22. Naim, A, Pan, Q, Baig, SM. Matrix metalloproteinases (MMPs) in liver diseases. J Clin Exp Hepatol 2017;74:367–72. https://doi.org/10.1016/j.jceh.2017.09.004.Suche in Google Scholar PubMed PubMed Central

23. Baenke, F, Peck, B, Miess, H, Schulze, A. Hooked on fat: the role of lipid synthesis in cancer metabolism and tumour development. Dis Model Mech 2013;6:1353–63. https://doi.org/10.1242/dmm.011338.Suche in Google Scholar PubMed PubMed Central

24. Bechmann, L, Hannivoort, R, Gerken, G, Hotamisligil, GS, Trauner, M, Canbay, A. The interaction of hepatic lipid glucose metabolism in liver diseases. J Hepatol 2012;56:952–64. https://doi.org/10.1016/j.jhep.2011.08.025.Suche in Google Scholar PubMed

25. Rae, C, Graham, A. Human resistin promotes macrophage lipid accumulation. Diabetolgia 2016;49:1112–4. https://doi.org/10.1007/s00125-006-0187-6.Suche in Google Scholar PubMed

26. Prasad, S, Gupta, S, Tyagi, A. Reactive oxygen species (ROS) and cancer: role of antioxidative nutraceuticals. Cancer Lett. 2017;387:95–105.10.1016/j.canlet.2016.03.042Suche in Google Scholar PubMed

27. Jiang, B. Aerobic glycolysis and high level of lactate in cancer metabolism and microenvironment. Genes Dis 2017;4:25–7. https://doi.org/10.1016/j.gendis.2017.02.003.Suche in Google Scholar PubMed PubMed Central

Received: 2022-06-24
Accepted: 2023-01-24
Published Online: 2023-03-03

© 2023 Walter de Gruyter GmbH, Berlin/Boston

Artikel in diesem Heft

  1. Frontmatter
  2. Original Articles
  3. The effect of encomir-93 mimic transfection on the expression of miR-93 and PSA and androgen receptor in prostate cancer LNcap cell line
  4. Association of S19W polymorphism in APOA5 gene and serum lipid levels in patients with type 2 diabetic nephropathy
  5. Examining the effect of Helicobacter pylori cagPAI variety on gene expression pattern related to gastric cancer
  6. Plasma IL-6, TREM1, uPAR, and IL6/IL8 biomarkers increment further witnessing the chronic inflammation in type 2 diabetes
  7. The effect of miR-372-5p regulation on CDX1 and CDX2 in the gastric cancer cell line
  8. Point-of-care salivary oxidative and renal functional markers to assess kidney function in reperfusion-induced acute kidney injury in male rats
  9. The differential role of resistin on invasive liver cancer cells
  10. The association of paraoxonase I gene polymorphisms Q192R (rs662) and L55M (rs854560) and its activity with metabolic syndrome components in fars ethnic group
  11. Metabolic syndrome – cardiac structure and functional analysis by echocardiography; a cross sectional comparative study
  12. Investigation of the relationship between betatrophin and certain key enzymes involved in carbohydrate and lipid metabolism in insulin-resistant mice
  13. Intermittent vs. continuous swimming training on adipokines and pro-inflammatory cytokines in metabolic syndrome experimental model
  14. Effect of four-week home-based exercise program on immune response, fat and muscle mass in subjects recovered from COVID-19
  15. Review Article
  16. Analytical and therapeutic profiles of DNA methylation alterations in cancer; an overview of changes in chromatin arrangement and alterations in histone surfaces
Heruntergeladen am 24.9.2025 von https://www.degruyterbrill.com/document/doi/10.1515/hmbci-2022-0063/html
Button zum nach oben scrollen