Forced Expressed GLP-1R Attenuates Prostate Cancer Growth

Abstract

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. Disclosure 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.