IntroductionIncretin-based therapy (like GLP-1R agonists) have been recently widely used as for treatment of diabetes and obesity. They have favourable effect on proliferation of beta cells of pancreas. GLP-1 mediates an incretin effect, by which oral glucose has a greater stimulatory effect on insulin secretion than intravenous glucose. GLP-1 binds to a specific GLP-1 receptor (GLP-1R), which is expressed in many tissues including; pancreatic beta cells, gastric mucosa, kidney, lung, heart, skin, immune cells, and the hypothalamus. In addition, those receptors are expressed in some types of cancers; including medullary thyroid, ovarian and colorectal cancers. The aim of our study is to explore the effect of GLP-1R agonist (exendin-4) and GLP-1 antagonist (exendin 9–39) on human pheochromocytoma (hPheo1) and colorectal cancer (HT29) cell proliferation and migration.Material and methodsGLP-1 receptor expression was detected by Western Blotting and real time PCR in 4 different cell lines; colorectal HT29, HCT116, [m1] pheochromocutoma (hPheo1) and neuroblastoma (SH-SY-5Y). Different concentrations (0.1–100 µM) of exendin-4 and exendin 9–39 (5 and 10 µM) were applied on hPheo1 and HT29 cell lines. The effect on proliferation was detected after 48 and 72 hours by cell viability assay (MTT). Cell migration assay was detected by wound healing experiment through measuring migration distance rate. Statistical significance was assessed using ANOVA, followed by post hoc Tukey Kramer test when groups were significantly different.Results and discussionsThe GLP1R gene is expressed in all 4 cell lines cell lines. Exendin-4 increased proliferation of hPheo and HT29 cell lines at 0.1μM and 1μM concentrations, as compared to control group (p<0.001). No proliferative effect was observed of exendin-4 at 10 μM, or exendin 9–39 in both hPheo1 and HT29 cell. Combination of exendin 4 and exendin 9–39 significantly decreased cell proliferation in both cell lines (p<0.001). There was no significant difference on cell migration distance rate after 24 hour-treatment of cells with either exendin-4 or exendin 9–39 or combination of both.ConclusionThe GLP-1R agonists may increase the proliferation of cancer cells initially and at low doses, whereas higher doses decreases the proliferation rate. They are likely to have no effect, or potentially favourable suppressing effect on cancer cell proliferation and migration in pheochromocytoma and colorectal cancer.