Chinese Journal of Endocrinology and Metabolism 2015;(6):530-534

doi:10.3760/cma.j.issn.1000-6699.2015.06.014

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

Rui WEI ; Jin YANG ; Tianpei HONG ; Hejun ZHAO ; Jing KE ; Wenfang HOU ; Ye LIU

Keywords

Glucagon-like peptide-1; Liraglutide; Human pancreatic cancer cells; Proliferation; Apoptosis

Country

China

Language

Chinese

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.