title: siRNA-mediated silencing of Notch-1 enhances docetaxel induced mitotic arrest and apoptosis in prostate cancer cells.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  Notch-1 promotes chemoresistance of prostate cancer and could be a potential therapeutic target.
authors.affiliation: Engineering and Technology Research Center for Transplantation Medicine of the National Ministry of Health, Hunan, China.
authors.forename: Qi-Fa
authors.initials: QF
authors.lastname: Ye
authors.forename: Yi-Chuan
authors.initials: YC
authors.lastname: Zhang
authors.forename: Xiao-Qing
authors.initials: XQ
authors.lastname: Peng
authors.forename: Zhi
authors.initials: Z
authors.lastname: Long
authors.forename: Ying-Zi
authors.initials: YZ
authors.lastname: Ming
authors.forename: Le-Ye
authors.initials: LY
authors.lastname: He
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D000077143:Docetaxel; D006801:Humans; D059566:M Phase Cell Cycle Checkpoints / Q000187:drug effects*; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000096:biosynthesis; D034622:RNA Interference; D034741:RNA, Small Interfering; D051881:Receptor, Notch1 / Q000235:genetics* / Q000378:metabolism*; D043823:Taxoids / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; C497761:NOTCH1 protein, human; D034741:RNA, Small Interfering; D051881:Receptor, Notch1; D043823:Taxoids; D000077143:Docetaxel; D051057:Proto-Oncogene Proteins c-akt