Exendin-4 inhibits growth and augments apoptosis of ovarian cancer cells

Mol Cell Endocrinol. 2016 Nov 15:436:240-9. doi: 10.1016/j.mce.2016.07.032. Epub 2016 Aug 3.

Abstract

Glucagon-like peptide (GLP)-1 promotes proliferation and survival in β-cell; however, whether GLP-1 receptor agonists promote growth of human ovarian cancer cells remain unknown. We aimed to explore the effects of GLP-1 agents on ovarian cancer cells. GLP-1 receptor expression in human ovarian cancer tissues was detected by immunohistochemical analysis. The effects of exendin-4, a GLP-1R agonist, were investigated on proliferation, migration and invasion, apoptosis in vitro and tumor formation in nude mice of ovarian cancer cells. Our study demonstrated that GLP-1R expressed in both human ovarian cancer tissues and cell lines. Exendin-4 inhibited growth, migration and invasion and enhanced apoptosis of ovarian cancer cells through inhibition of the PI3K/Akt pathway. And exendin-4 attenuated tumor formation by ovarian cancer cells in vivo. Our study suggests that GLP-1R agonists do not promote the growth of ovarian cancer and may even have anticancer effect on selected diabetic patients with ovarian cancer.

Keywords: Augments apoptosis; Exendin-4; Inhibit growth; Ovarian cancer cells.

MeSH terms

  • Adult
  • Aged
  • Animals
  • Apoptosis / drug effects*
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Exenatide
  • Female
  • Glucagon-Like Peptide-1 Receptor / metabolism
  • Humans
  • Mice, Nude
  • Middle Aged
  • Neoplasm Invasiveness
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology*
  • Peptides / pharmacology*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction / drug effects
  • Venoms / pharmacology*

Substances

  • Glucagon-Like Peptide-1 Receptor
  • Peptides
  • Venoms
  • Exenatide
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt