Wenjing He, Shuang Yu, Weisong Li, Haipeng Xiao
a Department of Endocrinology , The First Affiliated Hospital of Sun Yat-sen University , Guangzhou , China.
b Institute of Urology, The First Affiliated Hospital of Nanchang University , Nanchang , China.
Endocr Res. 2017 Aug;42(3):209-218. doi: 10.1080/07435800.2017.1292525. Epub 2017 Mar 20.
Glucagon-like peptide-1 (GLP-1) receptor agonists are a kind of very popular antidiabetes drugs. They promote cell proliferation and survival through activation of signaling pathways in human islet cells involving phosphate idylinositol 3 kinase (PI3K) and extracellular regulated kinases 1 and 2 (ERK1/2), which are frequently activated in human colon cancer cells. Then, it is possible that taking GLP-1 receptor (GLP-1R) agonists persistently would induce proliferation of β cells as well as colon cancer cells. So, clarifying the effects and mechanisms of GLP-1R agonists on colon cancer cells has important clinical implications.
We investigated GLP-1R expression in human colon cancer tissue samples with immunohistochemisty analysis and explored the effects of exendin-4, a GLP-1 receptor agonist, on colon cancer cells in vitro and in vivo.
The results showed lack of GLP-1R expression in both human colon cancer tissues and colon cancer cell lines. Exendin-4 did not enhance the proliferation and migration of colon cancer cell lines in vitro, and nor did it inhibit apoptosis induced by cytotoxic agents such as 5-fluorouracil (5-FU) or irinotecan. In addition, exendin-4 did not promote the propagation of colon cancer cells in vivo.
Our study suggests that GLP-1R agonists do not modify the growth or survival of human colon cancer cells and may be safe for diabetic patients with colon cancer.
胰高血糖素样肽-1（GLP-1）受体激动剂是一类非常受欢迎的抗糖尿病药物。它们通过激活人胰岛细胞中涉及磷脂酰肌醇3激酶（PI3K）和细胞外调节激酶1和2（ERK1/2）的信号通路来促进细胞增殖和存活，而这些信号通路在人结肠癌细胞中经常被激活。那么，持续服用GLP-1受体（GLP-1R）激动剂可能会诱导β细胞以及结肠癌细胞的增殖。因此，阐明GLP-1R激动剂对结肠癌细胞的作用及机制具有重要的临床意义。
我们通过免疫组织化学分析研究了人结肠癌组织样本中GLP-1R的表达，并在体外和体内探索了GLP-1受体激动剂艾塞那肽-4对结肠癌细胞的影响。
结果显示人结肠癌组织和结肠癌细胞系中均缺乏GLP-1R表达。艾塞那肽-4在体外并未增强结肠癌细胞系的增殖和迁移，也未抑制由5-氟尿嘧啶（5-FU）或伊立替康等细胞毒性药物诱导的细胞凋亡。此外，艾塞那肽-4在体内并未促进结肠癌细胞的增殖。
我们的研究表明，GLP-1R激动剂不会改变人结肠癌细胞的生长或存活，对于患有结肠癌的糖尿病患者可能是安全的。
