Glucagon-like peptide (GLP)-1 promotes proliferation and survival in b-cell; however, whether GLP-1 receptor agonists promote growth of human ovarian cancer and colon cancer cells remain unknown.
We aimed to explore the expression of GLP-1 receptor (GLP-1R) in ovarian cancer and colon cancer tissues and the effects of exendin-4，a GLP-1R agonist, on growth, migration, invasion and apoptosis of ovarian cancer and colon cancer cells in vitro and in vivo, in addition, we further explore the molecular mechanisms involved.
We detected GLP-1R expression in 90 cases of human ovarian cancer and 20 cases of normal ovarian tissue samples，and 30 cases of human colon cancer and 20 cases of normal colon tissue samples by immunohistochemical analysis. The effects of exendin-4 were investigated on proliferation, migration and invasion, apoptosis in vitro and tumor formation in nude mice of ovarian and colon cancer cells. The PI3K/Akt pathway and MAPK-ERK1/2 pathway, which are two classic signaling pathways of GLP-1R activation in pancreatic β-cells, were assessed in the study.
We found that GLP-1R expressed in human ovarian cancer and normal ovarian tissues.Exendin-4 inhibited growth, migration and invasion, and enhanced apoptosis of ovarian cancer cells in vitro through inhibiting AKT activation and, subsequently, up-regulation of E-cadherin and caspase-3 cleavage (c-cas-3). The antitumor effects are GLP-1R dependent. Consistent with the in vitro results, exendin-4 attenuated tumor formation by ovarian cancer cells in nude mice. While the results showed lack of GLP-1R expression in both human colon cancer tissues and colon cancer cell lines. Ex-4 did not modulate the proliferation of these cell lines in vitro, and nor did it inhibit apoptosis after exposure to cytotoxic agent. In addition, Ex-4 did not promote the propagation of colon cancer cells in vivo.
Our study suggests that GLP-1R agonists at least do not promote the growth of ovarian cancer and colon cancer, and they may even have anticancer effects on selected diabetic patients with ovarian cancer.