Silodosin inhibits prostate cancer cell growth via ELK1 inactivation and enhances the cytotoxic activity of gemcitabine

摘要: BACKGROUND Biological significance of ELK1, a transcriptional factor whose phosphorylation is necessary for c-fos proto-oncogene activation, in prostate cancer remains far from fully understood. In this study, we aim to investigate the role ELK1 tumor growth as well efficacy selective α1A-adrenergic blocker, silodosin, activity cells. METHODS We first immunohistochemically determined levels phospho-ELK1 (p-ELK1) expression radical prostatectomy specimens. We then assessed effects knockdown via short hairpin RNA and silodosin on cell proliferation, migration, invasion lines. RESULTS The p-ELK1 were significantly higher carcinoma than benign (P < 0.001) or high-grade prostatic intraepithelial neoplasia (HGPIN) (P = 0.002) HGPIN (P < 0.001). Kaplan–Meier log-rank tests revealed that moderate-strong positivity carcinomas tended correlate with biochemical recurrence after (P = 0.098). PC3 DU145 expressing (mRNA/protein) but no androgen receptor (AR), silencing resulted considerable decreases migration/invasion matrix metalloproteinase-2 expression, not viability. Silodosin treatment reduced expression/activity these cells viability AR-positive LNCaP C4-2 migration both AR-negative cells, ELK1-negative cells. Interestingly, increased sensitivity gemcitabine, cisplatin docetaxel, even cells. CONCLUSIONS ELK1 likely be activated promote progression. Furthermore, inactivates only inhibits their also enhances cytotoxic gemcitabine. Thus, inhibition has potential being therapeutic approach cancer. Prostate 76:744–756, 2016. © 2016 Wiley Periodicals, Inc.