title: Resistance to docetaxel-induced apoptosis in prostate cancer cells by p38/p53/p21 signaling.
abstract: BACKGROUND
  Taxane chemotherapy is one of the few therapeutic options for men with castration-resistant prostate cancer. However, the working mechanisms are not fully understood. We aimed to investigate the possible molecular mechanism of apoptosis induced by taxanes in prostate cancer.
  
  
  METHODS
  The human LNCaP cells (bearing wild-type p53), DU145 cells (bearing mutant p53) and PC3 cells (lacking p53) were used. The expression levels of protein were determined by Western blot and the mRNA levels were determined by reverse transcriptase PCR. The apoptosis was measured by propidium iodide (PI) staining and flow cytometric analysis.
  
  
  RESULTS
  LNCaP cells are more resistant to docetaxel than DU145 and PC3 cells. Knocking down p53 by small interference RNA (siRNA) sensitizes LNCaP cells to docetaxel treatment. Docetaxel stabilizes p53 protein level and upregulates p21 in a p53-dependent manner in LNCaP cells. Docetaxel increases p38 phosphorylation in LNCaP cells. Treatment with p38-specific inhibitor SB203580 or knocking down p38 by siRNA significantly impaired the upregulation of p53 and p21 by docetaxel. Knocking down p38 or p21 sensitizes LNCaP cells to docetaxel treatment and the antiapoptotic effect of p21 can be reversed by p38 siRNA in LNCaP cells.
  
  
  CONCLUSIONS
  Stimulation of the p38/p53/p21 signaling axis could be important for regulating the susceptibility towards docetaxel in prostate cancer.
authors.affiliation: College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China. lugan@mail.hust.edu.cn
authors.forename: Lu
authors.initials: L
authors.lastname: Gan
authors.forename: Jianlin
authors.initials: J
authors.lastname: Wang
authors.forename: Huibi
authors.initials: H
authors.lastname: Xu
authors.forename: Xiangliang
authors.initials: X
authors.lastname: Yang
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D045744:Cell Line, Tumor; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D043823:Taxoids / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors / Q000502:physiology*; D054462:p21-Activated Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*
chemical_list: D043823:Taxoids; D016159:Tumor Suppressor Protein p53; D000077143:Docetaxel; D054462:p21-Activated Kinases; D048051:p38 Mitogen-Activated Protein Kinases