利拉鲁肽对人胰腺癌细胞增殖和凋亡的影响及可能机制  

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

作　　者：魏蕊[1] 杨进[1] 洪天配[1] 赵荷珺[1] 柯静[1] 侯文芳[1] 刘烨[1] 

机构地区：[1]北京大学第三医院内分泌科,100191

出　　处：《中华内分泌代谢杂志》2015年第6期530-534,共5页Chinese Journal of Endocrinology and Metabolism

基　　金：国家自然科学基金资助项目（81400798,81400767,81401142）：高等教育博士学科点新教师基金资助项目（20120001120069,20120001120076,20120001120063）

摘　　要：目的：观察胰升糖素样肽1（GLP-1）受体激动剂利拉鲁肽对人胰腺癌细胞增殖和凋亡的影响,并初步探讨可能的作用机制。方法体外培养的人胰腺癌细胞系 MIA PaCa-2应用10~1000 nmol/ L利拉鲁肽干预24 h 或100 nmol/ L 利拉鲁肽干预0~72 h。 CCK-8试剂盒检测细胞增殖,RT-PCR 和 Western印迹检测相关基因的 mRNA 和蛋白表达水平。结果 MIA PaCa-2细胞系表达 GLP-1受体。利拉鲁肽可剂量和时间依赖性抑制胰腺癌细胞增殖,上调促凋亡蛋白 Bax 的表达,抑制抗凋亡蛋白 Bcl2的表达。同时,利拉鲁肽还可剂量和时间依赖性抑制胰腺癌细胞的胰岛素受体（ INSR）和胰岛素样生长因子1受体（IGF-1R）的表达,并且抑制下游信号分子 Erk1/2和 Akt 蛋白的磷酸化水平。结论利拉鲁肽可抑制人胰腺癌细胞增殖和促进其凋亡,其抑癌效应可能是通过下调 INSR 和 IGF-1R 的表达,继而抑制 MEK/ Erk1/2和 PI3k/ Akt 信号通路所介导的。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.

关 键 词：胰升糖素样肽 1 利拉鲁肽 人胰腺癌细胞 增殖 凋亡 

分 类 号：R735.9[医药卫生—肿瘤]