研究課題
Aim:. Here, we examined the relationship between human prostate cancer severity and GLP-1R expression, as well as the effect of forced expression of GLP-1R using a lentiviral vector.Methods: Prostate cancer tissues were extracted by prostatectomy and biopsy. GLP-1R was overexpressed in ALVA-41 cells using a lentiviral vector (ALVA-41-GLP-1R cells). GLP-1R expression was detected by immunohistochemistry and quantitative PCR. Cell proliferation was examined by growth curves and BrdU incorporation assays. Cell cycle distribution and regulators were examined by flow cytometry and western blotting. In vivo experiments were performed using a xenografted model. Results:GLP-1R expression levels were significantly inversely associated with the Gleason score of human prostate cancer tissues. Abundant GLP-1R expression and functions were confirmed in ALVA-41-GLP-1R cells. Exendin-4 significantly decreased ALVA-41-GLP-1R cell proliferation in a dose-dependent manner. DNA synthesis and G1-to-S phase transition were inhibited in ALVA-41-GLP-1R cells. SKP2 expression was decreased and p27Kip1 protein was subsequently increased in ALVA-41-GLP-1R cells treated with exendin-4. In vivo experiments performed by implanting ALVA-41-GLP-1R cells demonstrated that exendin-4 decreased prostate cancer growth by activation of GLP-1R overexpressed in ALVA41-GLP-1R cells. Conclusions: Forced expression of GLP-1R attenuates prostate cancer cell proliferation by inhibiting cell cycle progression in vitro and in vivo. Therefore, GLP-1R activation may be a potential therapy for prostate cancer.
1: 当初の計画以上に進展している
論文投稿済み。Journal of Diabetes Investigationにアクセプトされた。
本研究を広く世間に通達する活動を行うとともに、今後の新たな研究発展に繋がるヒント模索する。
すべて 2020
すべて 雑誌論文 (1件) (うち査読あり 1件、 オープンアクセス 1件)
Journal of Diabetes Investigation
巻: NA ページ: NA
10.1111/jdi.13247.
