Effect and mechanism of liraglutide on proliferation and apoptosis of human pancreatic cancer cells

Abstract

Objective To investigate the effects and mechanism of glucagon-like peptide-1(GLP-1)receptor agonist liraglutide on the proliferation and apoptosis of human pancreatic cancer cells. Methods The human pancreatic cancer cell line MIA PaCa-2 was incubated for 24 h with liraglutide at various concentrations(10-1 000 nmol/L), or with 100 nmol/L liraglutide for various durations(0-72 h). Cell proliferation was determined by Cell Counting Kit-8(CCK-8)analysis. RT-PCR and Western blot were used to detect the mRNA and protein expression levels of related genes. Results GLP-1 receptor was expressed in the MIA PaCa-2 cells. Liraglutide suppressed cell proliferation, up-regulated the expression levels of pro-apoptotic protein Bax and down-regulated the expression levels of anti-apoptotic protein Bcl2 in human pancreatic cancer cells in a dose- and time-dependent manner. Meanwhile, liraglutide down-regulated the expression levels of insulin receptor(INSR)and insulin-like growth factor-1 receptor(IGF-1R), and the phosphorylation levels of their downstream signaling proteins Erk1/2 and Akt, in a dose- and time-dependent way. Conclusion Liraglutide inhibits proliferation and promotes apoptosis of human pancreatic cancer cells; the process may be mediated via suppressing the expression of INSR and IGF-1R and inhibiting activation of the downstream MEK/Erk1/2 and PI3k/Akt pathways. (Chin J Endocrinol Metab, 2015, 31: 530-534) Key words: Glucagon-like peptide-1; Liraglutide; Human pancreatic cancer cells; Proliferation; Apoptosis