PC 12. Down - regulation of Notch-1 enhances docetaxel - induced mitotic arrest and apoptosis in prostate cancer cells

Background: Notch is an ancient cell signaling system that regulates cell fate, stem cell maintenance and the initiation of differentiation in many tissues. It has been reported that activation of Notch-1 may increase chemoresistance in breast cancer and lung cancer. Therefore, the down-regulation of Notch-1 protein levels may enhance chemotherapy efficacy in solid tumors. The aim of this study was to investigate the effects of Notch-1 silencing on docetaxel treatment in prostate cancer cells.

Materials and Methods: Multiple cellular and molecular approaches, such as siRNA transfections, MTT assays, flow cytometry, real-time RT-PCR and Western blotting, were used with PC-3 prostate cancer cells.

Results: Our results showed that down-regulation of Notch-1 before docetaxel treatment in prostate cancer cells resulted in cell growth inhibition, G2/M phase cell cycle arrest. In addition, we found that these effects were associated with increased p21waf1/ cip1 expression and decreased Akt and p-Akt activity regulated by Notch-1.

Conclusions: These results suggest that Notch-1 could be a potential therapeutic target for the treatment of prostate cancer.