sildenafil-citrate has been researched along with Prostatic-Neoplasms--Castration-Resistant* in 1 studies
1 other study(ies) available for sildenafil-citrate and Prostatic-Neoplasms--Castration-Resistant
Article | Year |
---|---|
Sildenafil Potentiates the Therapeutic Efficacy of Docetaxel in Advanced Prostate Cancer by Stimulating NO-cGMP Signaling.
Docetaxel plays an indispensable role in the management of advanced prostate cancer. However, more than half of patients do not respond to docetaxel, and those good responders frequently experience significant cumulative toxicity, which limits its dose duration and intensity. Hence, a second agent that could increase the initial efficacy of docetaxel and maintain tolerability at biologically effective doses may improve outcomes for patients.. We determined phosphodiesterase 5 (PDE5) expression levels in human and genetically engineered mouse (GEM) prostate tissues and tumor-derived cell lines. Furthermore, we investigated the therapeutic benefits and underlying mechanism of PDE5 inhibitor sildenafil in combination with docetaxel using. PDE5 expression was higher in both human and mouse prostate tumors and cancer cell lines compared with normal tissues/cells. In GEM prostate-derived cell lines, PDE5 expression increased from normal prostate (wild-type) epithelial cells to androgen-dependent and castrated prostate-derived cell lines. The addition of physiologically achievable concentrations of sildenafil enhanced docetaxel-induced prostate cancer cell growth inhibition and apoptosis. Our results demonstrate that sildenafil's addition could sensitize docetaxel chemotherapy in prostate cancer cells at much lesser concentration than needed for inducing cell death. Thus, the combinatorial treatment of sildenafil and docetaxel may improve anticancer efficacy and reduce chemotherapy-induced side-effects among patients with advanced prostate cancer. Topics: Androgens; Animals; Apoptosis; Cell Line, Tumor; Cyclic AMP; Cyclic Nucleotide Phosphodiesterases, Type 5; Disease Models, Animal; Docetaxel; Drug Synergism; Epithelial Cells; Gene Expression Regulation, Neoplastic; Heterografts; Humans; Male; Mice; Mice, Knockout; Nitric Oxide; Prostatic Neoplasms, Castration-Resistant; Signal Transduction; Sildenafil Citrate | 2020 |