Effect and mechanism of liraglutide on proliferation and apoptosis of human pancreatic cancer cells
10.3760/cma.j.issn.1000-6699.2015.06.014
- VernacularTitle:利拉鲁肽对人胰腺癌细胞增殖和凋亡的影响及可能机制
- Author:
Rui WEI
;
Jin YANG
;
Tianpei HONG
;
Hejun ZHAO
;
Jing KE
;
Wenfang HOU
;
Ye LIU
- Publication Type:Journal Article
- Keywords:
Glucagon-like peptide-1;
Liraglutide;
Human pancreatic cancer cells;
Proliferation;
Apoptosis
- From:
Chinese Journal of Endocrinology and Metabolism
2015;(6):530-534
- CountryChina
- 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.
