Rho kinase 2 promotes epithelial-mesenchymal transition and proliferation in human prostate cancer PC-3 cells.

Prostate cancer is the second most common cancer in men. Although androgen deprivation therapy is initially effective, resistance inevitably develops. Most patients eventually progress to castration-resistant prostate cancer, a stage with limited treatment options and poor prognosis. Rho kinases (ROCK1 and ROCK2) have been implicated in cancer progression, but their therapeutic targeting remains limited. This study examined the pathological roles of ROCK1 and ROCK2 in epithelial-mesenchymal transition (EMT) and proliferation of prostate cancer cells. ROCK1 expression was comparable between human prostate epithelial cells (PrECs) and androgen-independent prostate cancer cells, PC-3 and DU145. In contrast, ROCK2 expression was higher in PC-3 cells than in PrECs and DU145 cells. EMT marker analysis revealed that PC-3 cells exhibited decreased E-cadherin and increased N-cadherin and Snail expression. ROCK2 knockdown reversed this EMT phenotype, reducing cell proliferation, migration, 3D tumor spheroid formation, and spheroid cell viability. Similar inhibitory effects were observed by the ROCK2-selective blocker KD025 (IC = 422 nM). Furthermore, ROCK2 deficiency attenuated the tumor growth of PC-3 cells in a xenograft mouse model. These findings indicate that ROCK2 promotes EMT process and tumor progression in PC-3 cells. Targeting ROCK2 may represent a promising therapeutic strategy for androgen-independent prostate cancer.