Li X-N, Bu H-M, Ma X-H, Lu Sh, Zhao Sh, Cui Y-L, Sun J
The Health Management Center, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Department of Endocrinology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Exp Clin Endocrinol Diabetes. 2017 Feb;125(2):91-97. doi: 10.1055/s-0042-112368. Epub 2016 Dec 22.
Research has shown that the incidence of prostate cancer is increased in patients with type 2 diabetes mellitus (T2DM) 1. Glucagon-like peptide-1 (GLP-1) is a gastrointestinal hormone that enhances glucose-dependent insulin secretion and suppresses glucagon release. Here, we examined the effect of exenatide and liraglutide, 2 types of GLP-1 analogues, on prostate cancer cells growth by CCK-8 assay, Hoechst33258 staining assay, and western blot analysis of apoptosis-related proteins Bax and Bcl-2. Also the kinase pathways maybe involved and the expression of GLP-1 receptor (GLP-1 R) in LNCap cells was detected. In our experiments, exenatide and liraglutide significantly inhibited the proliferation of the LNCap cell lines and induced the cell apoptosis. Exenatide (1-100 nmol/L) increased the ratio of Bax/Bcl-2 in a dose-dependent manner, whereas liraglutide increased Bax/Bcl-2 ratio only at concentrations of 10 nmol/L. And we found that GLP-1 analogues activate p38 but not ERK1/2 or AKT in LNCap cells. And classical GLP-1 receptor was detected in LNCap cells. These data suggest that exenatide and liraglutide attenuate prostate cancer growth through regulating P38 pathway by binding with GLP-1R.
研究表明，2型糖尿病（T2DM）患者前列腺癌的发病率会升高[1]。胰高血糖素样肽-1（GLP-1）是一种胃肠激素，可增强葡萄糖依赖性胰岛素分泌并抑制胰高血糖素释放。在此，我们通过CCK-8检测、Hoechst33258染色检测以及凋亡相关蛋白Bax和Bcl-2的蛋白质印迹分析，研究了两种GLP-1类似物艾塞那肽和利拉鲁肽对前列腺癌细胞生长的影响。此外，还检测了可能涉及的激酶途径以及LNCap细胞中GLP-1受体（GLP-1R）的表达。在我们的实验中，艾塞那肽和利拉鲁肽显著抑制LNCap细胞系的增殖并诱导细胞凋亡。艾塞那肽（1 - 100 nmol/L）以剂量依赖性方式增加Bax/Bcl-2的比率，而利拉鲁肽仅在浓度为10 nmol/L时增加Bax/Bcl-2比率。并且我们发现GLP-1类似物在LNCap细胞中激活p38，但不激活ERK1/2或AKT。在LNCap细胞中检测到经典的GLP-1受体。这些数据表明，艾塞那肽和利拉鲁肽通过与GLP-1R结合调节P38途径来减弱前列腺癌的生长。
