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Inhibition of PI3K/Akt and ERK signaling decreases visfatin-induced invasion in liver cancer cells

  • Candace Miethe , Linda Torres , Megan Zamora and Ramona S. Price EMAIL logo
Published/Copyright: August 27, 2021
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Hormone Molecular Biology and Clinical Investigation
From the journal Hormone Molecular Biology and Clinical Investigation Volume 42 Issue 4

Abstract

Objectives

Visfatin is found in adipose tissue and is referred to as nicotinamide phosphoribosyltransferase (Nampt). Visfatin has anti-apoptotic, proliferative, and metastatic properties and may mediate its effects via ERK and PI3K/Akt signaling. Studies have yet to determine whether inhibition of kinase signaling will suppress visfatin-induced liver cancer. The purpose of this study was to determine which signaling pathways visfatin may promote liver cancer progression.

Methods

HepG2 and SNU-449 liver cancer cells were exposed to visfatin with or without ERK or PI3K/Akt inhibitor, or both inhibitors combined. These processes that were assessed: proliferation, reactive oxygen species (ROS), lipogenesis, invasion, and matrix metalloproteinase (MMP).

Results

Inhibition of PI3K/Akt and combination of inhibitors suppressed visfatin-induced viability. ERK inhibition in HepG2 cells decreased visfatin-induced proliferation. ERK inhibitor alone or in combination with PI3K inhibitors effectively suppressed MMP-9 secretion and invasion in liver cancer cells. PI3K and ERK inhibition and PI3K inhibition alone blocked visfatin’s ROS production in SNU-449 cells. These results corresponded with a decrease in phosphorylated Akt and ERK, β-catenin, and fatty acid synthase.

Conclusions

Akt and ERK inhibition differentially regulated physiological changes in liver cancer cells. Inhibition of Akt and ERK signaling pathways suppressed visfatin-induced invasion, viability, MMP-9 activation, and ROS production.

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

Funding source: Texas State University

  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 is not related either human or animal use.

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Supplementary Material

The online version of this article offers supplementary material (DOI: https://doi.org/10.1515/hmbci-2021-0011).

Received: 2021-02-10
Accepted: 2021-07-13
Published Online: 2021-08-27

© 2021 Walter de Gruyter GmbH, Berlin/Boston

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https://doi.org/10.1515/hmbci-2021-0011
Keywords for this article
Akt; ERK; liver cancer; obesity; visfatin

Articles in the same Issue

  1. Frontmatter
  2. Letters to the Editor
  3. The solution to obesity and type 2 diabetes: reversing insulin resistance
  4. The second wave of COVID-19: effect on Indian health care system
  5. Original Articles
  6. Association between vitamin D level and prognostic factors among patients infected with SARS-CoV-2
  7. The association between serum vitamin D and mood disorders in a cohort of lipedema patients
  8. Inhibition of PI3K/Akt and ERK signaling decreases visfatin-induced invasion in liver cancer cells
  9. The outcome of intra-cytoplasmic sperm injection (ICSI): do the sperm concentration and motility matter?
  10. Effect of two hypercaloric diets on the hormonal and metabolic profile of the adrenal gland
  11. Investigation of the effect of training on serotonin, melatonin and hematologic parameters in adolescent basketball players
  12. A fine tuning of embryo loading technique by eliminating the air bubble in the outer sheath of embryo catheter among women undergoing IVF treatment
  13. Effects of different doses of melatonin on rat adipose derived mesenchymal stem cells
  14. PTEN protein expression has role in predicting disease-free-interval in endometrioid endometrial carcinoma
  15. Amelioration of STZ-induced nephropathy in diabetic rats by saffron hydro alcoholic extract
  16. Elevated levels of neopterin and pentraxin 3 in patients with rheumatoid arthritis
  17. Case Reports
  18. COVID-19 transmission: a positive perspective
  19. Distant recurrence of endometrial cancer more than 10 years after hysterectomy: a case report
  20. Review Articles
  21. COVID-19 and lung pathologies
  22. Potential role of melatonin in prevention and treatment of leukaemia
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