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siRNA-mediated Silencing of Notch-1 Enhances Docetaxel Induced Mitotic Arrest and Apoptosis in PCa Cells

  • Ye, Qi-Fa (Engineering and Technology Research Center for Transplantation Medicine of the National Ministry of Health) ;
  • Zhang, Yi-Chuan (Engineering and Technology Research Center for Transplantation Medicine of the National Ministry of Health) ;
  • Peng, Xiao-Qing (Department of Gastroenterology, The Third Xiangya Hospital, Central South University) ;
  • Long, Zhi (Department of Urology, The Third Xiangya Hospital, Central South University) ;
  • Ming, Ying-Zi (Engineering and Technology Research Center for Transplantation Medicine of the National Ministry of Health) ;
  • He, Le-Ye (Department of Urology, The Third Xiangya Hospital, Central South University)
  • Published : 2012.06.30

Abstract

Purpose: Notch is an important signaling pathway that regulates cell fate, stem cell maintenance and the initiation of differentiation in many tissues. It has been reported that activation of Notch-1 contributes to tumorigenesis. However, whether Notch signaling might have a role in chemoresistance of prostate cancer is unclear. This study aimed to investigate the effects of Notch-1 silencing on the sensitivity of prostate cancer cells to docetaxel treatment. Methods: siRNA against Notch-1 was transfected into PC-3 prostate cancer cells. Proliferation, apoptosis and cell cycle distribution were examined in the presence or absence of docetaxel by MTT and flow cytometry. Expression of $p21^{waf1/cip1}$ and Akt as well as activation of Akt in PC-3 cells were detected by Western blot and Real-time PCR. Results: Silencing of Notch-1 promoted docetaxel induced cell growth inhibition, apoptosis and cell cycle arrest in PC-3 cells. In addition, these effects were associated with increased $p21^{waf1/cip1}$ expression and decreased Akt expression and activation in PC-3 cells. Conclusion: Notch-1 promotes chemoresistance of prostate cancer and could be a potential therapeutic target.

Keywords

Notch signaling;prostate cancer;siRNA;cell cycle;apoptosis;$p21^{waf1/cip1}$;Akt

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