Incretin therapy is one of the most popular treatment for type 2 diabetes. GLP-1R agonist has received much attention, because of its tissue protective effects beyond glycemic control. We have previously reported anti-prostate and anti-breast cancer effect of GLP-1R agonist Exendin-4(Ex-4) (Diabetes 2014, PLOS ONE 2015, Endocrinology 2017). In our previous report, the attenuation of cancer cell proliferation was depending on GLP-1R expression, and Ex-4 did not attenuate cell proliferation in ALVA-41, prostate cancer cell line without GLP-1R expression. Then, we next examined anti-prostate cancer effect in ALVA-41 forced expressed GLP-1R using lentivirus vector (ALVA-41-GLP-1R). We confirmed abundant GLP-1R expression in ALVA-41-GLP-1R using RT-PCR and immunohistochemistry. Ex-4 significantly decreased the proliferation of ALVA-41-GLP-1R in a dose dependent manner, but not in ALVA-41 transfected with control vector (ALVA-41-control), suggesting that forced expressed GLP-1R was intact. In the growth curve, cell number of ALVA-41-GLP-1R was significantly decreased compared with ALVA-41-control. BrdU assay revealed that cell proliferation was attenuated in ALVA-41-GLP-1R, and S Phase entry was inhibited in cell cycle distribution. Further, p27(CDKN1B) expression was increased in ALVA-41-GLP-1R compared with ALVA-41-control in Western Blotting analysis. These data suggest that forced expressed GLP-1R attenuated prostate cancer cell proliferation via inhibiting cell cycle progression.


T. Shigeoka: None. T. Nomiyama: Research Support; Self; MSD K.K., Sanofi-Aventis, Boehringer Ingelheim Pharmaceuticals, Inc., Takeda Pharmaceuticals, Japan. T. Kawanami: None. Y. Hamaguchi: None. T. Tanaka: None. T. Yanase: Research Support; Self; MSD K.K., Boehringer Ingelheim Pharmaceuticals, Inc., Takeda Pharmaceuticals, Japan.

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at