Exendin-4 does not modify growth or apoptosis of human colon cancer cells

Aim: 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. Materials and methods: 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. Results: 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. Conclusion: 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.

研究目的：胰高血糖素样肽-1（GLP-1）受体激动剂是一类热门的抗糖尿病药物，其可通过激活人类胰岛细胞内的磷脂酰肌醇3激酶（PI3K）与细胞外调节蛋白激酶1和2（ERK1/2）信号通路，促进细胞增殖与存活；而这两条通路在人类结肠癌细胞中常被激活。因此，长期使用GLP-1受体激动剂或可同时诱导胰岛β细胞与结肠癌细胞的增殖，阐明GLP-1受体激动剂对结肠癌细胞的作用及机制具有重要的临床意义。
材料与方法：本研究采用免疫组织化学分析法检测人类结肠癌组织样本中GLP-1受体的表达情况，并探讨GLP-1受体激动剂艾塞那肽（exendin-4）对结肠癌细胞的体内外作用。
结果：结果显示，人类结肠癌组织及结肠癌细胞系均未检测到GLP-1受体的表达。艾塞那肽在体外既未促进结肠癌细胞系的增殖与迁移，也未抑制由5-氟尿嘧啶（5-FU）、伊立替康（irinotecan）等细胞毒性药物诱导的细胞凋亡。此外，艾塞那肽在体内也未促进结肠癌细胞的增殖。
结论：本研究表明，GLP-1受体激动剂不会改变人类结肠癌细胞的生长或存活状态，对于合并结肠癌的糖尿病患者可能具有安全性。