The Inhibitory Effect of Roscovitine on Prostate Cancer Cell Proliferation and Androgen Receptor Phosphorylation

Fu-Ning Hsu ； Wei-Hsiang Kao ； Pao-Hsuan Huang ； Ching-Han Yu ； Hsin-Yi Wang ； Kun-Yuan Chiu ； Tsung-Ying Yang ； Chieh-Lin Jerry Teng ； Kun-Chien Chen ； Ho Lin ； Chih-Ho Lai ； Jer-Tsong Hsieh ； Mei-Chih Chen

《Adaptive Medicine》 10卷1期 (2018/03) Pp. 34-42

https://doi.org/10.4247/AM.2018.ABI198

摘要

It has been reported that ccyclin-dependent kinases (CDKs) play important roles in modulating androgen receptor (AR) function and prostate cancer cell growth. Roscovitine is a CDK inhibitor and had been applied in clinical trials in some types of cancer. The aim of this study is to investigate the role of AR phosphorylation in Roscovitine-induced inhibition of prostate cancer cell growth. The results indicated that Roscovitine treatment significantly inhibited the growth of both prostate cancer cell lines and normal prostatic cells. The result of xenografted tumor growth also support the finding. The induces of AR activation, including subcellular localization, promoter activity, and prostate specific antigen (PSA) production/secretion, were all inhibited after Roscovitine treatment. Besides, there was no additive effect of Roscovitine with AR inhibitor (Bicalutamide) treatment on LNCaP cell growth. It suggests that Roscovitine and AR inhibitor might share similar mechanism on inhibiting prostate cancer cell growth. In summary, AR might be one of the pharmaceutical targets of Roscovitine on inhibiting prostate cancer cells and can be used in future basic research as well as clinical application.

關鍵字

androgen receptor ； cell proliferation ； prostate cancer ； Roscovitine