Abstract
Although docetaxel-based chemotherapy is therapeutically efficacious, drug resistance often leads to treatment failure in castration-resistant prostate cancer patients. The Notch signaling pathway plays a key role in prostate development and prostate cancer. We investigated whether silencing Notch-1 has therapeutic potential for the treatment of prostate cancer. To determine this, we performed cell and molecular analyses following the silencing of the Notch-1 gene in PC-3 castration-resistant prostate cancer cells using small interfering RNA. The results demonstrated that silencing the Notch-1 gene effectively inhibits proliferation and induces apoptosis in PC-3 cells. In addition, docetaxel treatment results in decreased proliferation and increased apoptosis in the Notch-1-silenced cells compared to the control PC-3 cells. Docetaxel treatment was also accompanied by an upregulation of Bax and a downregulation of Bcl-2. Thus, Notch-1 silencing downregulates the anti-apoptotic protein Bcl-2, and upregulates the pro-apoptotic protein Bax, which ultimately results in increased sensitivity of PC-3 cells to docetaxel. Taken together, these results suggest that Notch-1 is potentially an effective target for treating castration-resistant prostate cancer.