Simvastatin-Mediated Inhibition Of Prostate Cancer. Molecular Mechanisms Regulating Cellular Functions In-Vitro And Tumor Growth In-Vivo

      Аннотация: Prostate cancer is a leading cause of death in USA. Proper management of disease requires better understanding of mechanisms involved in cancer growth and proliferation. Statins were shown to have beneficial effects in cancers, as proven by the many clinical trials supporting the evidence. Our research studied simvastatin effects and molecular mechanisms affecting prostate cancer in vitro and in vivo. We showed that simvastatin affected proliferation, colony formation and migration, in both androgen-dependent and –independent human prostate cancer. In vivo effects were supportive with a reduction of tumor size in proper experimental models. Mechanisms of effect of simvastatin on cancer cell micrometastasis were also studied using ECIS, gene arrays, adhesion assays immunocytochemistry and western blotting and showed its effects on integrin and endothelial barrier. The effect of combining simvastatin with docetaxel was also studied and showed promising results. In conclusion, our pre-clinical research shows beneficial effect of simvastatin alone or in combination with docetaxel in the management of prostate cancer and prevention of micrometastasis.

Ключевые слова: Prostate Cancer, tumor, Inhibition, molecular mechanisms, Simvastatin, Cellular functions