title: [The effect of cell killing by ABT-737 synergized with docetaxel in human prostate cancer PC-3 cells].
abstract: OBJECTIVE
  To investigate the synergistical killing effect of docetaxel combined with ABT-737 on human prostate cancer cell line PC-3 by inducing apoptosis and further to determine the mechanism underlying such effect.
  
  
  METHODS
  PC-3 cells were treated with various concentrations of docetaxel or (and) ABT-737. Cell viability was determined using MTT assay. Apoptosis was assessed by fluorescence microscopy analysis of cells with condensed and segmented nuclei following staining with 4',6-diamidino-2-phenylindole (DAPI). Cellular DNA was stained with propidium iodide and flow cytometric analysis was performed to analyze the cell cycle distribution. Bcl-2, Bax, Bcl-xL and Mcl-1 protein changes were detected by Western blot. The activity of caspase-3 was measured using a colorimetric assay.
  
  
  RESULTS
  Docetaxel (20 nmol/L) combination with ABT-737 (400 nmol/L) for 48 hours, the cell viability was decreased to 19.7% ± 3.2% to compare with 44.2% ± 4.4% (t = 4.45) of docetaxel and 93.2% ± 1.8% of ABT-737 separately and there was a synergistic effect between the two drugs (CI = 0.8). Apoptosis rate of the combination group was higher than other two drugs. Docetaxel increased the cell number arrested in G(2)/M phase compared with control group (P < 0.05), but the combination treatment resulted in a significant arrest in the G(0)/G(1) phase. The combination treatment could significantly reduced the Bcl-2, Bcl-xL and Mcl-1 expression (F = 369.53, 57.89 and 32.77, all P < 0.05) and enhanced the activity of caspase-3 (419.7% ± 15.6%) (F = 207.33, P < 0.05).
  
  
  CONCLUSIONS
  The combination of ABT-737 with docetaxel can synergistically inhibit the proliferation of PC-3 cells through inducing apoptosis, which may be associated with cell cycle arrest, down-regulation of Bcl-2, Bcl-xL and Mcl-1 expression and activation of caspase-3.
authors.affiliation: Department of Urology, the People's Hospital of Henan Province, Zhengzhou 450003, China.
authors.forename: Jian-wei
authors.initials: JW
authors.lastname: Hao
authors.forename: Xiao-peng
authors.initials: XP
authors.lastname: Mao
authors.forename: De-gang
authors.initials: DG
authors.lastname: Ding
authors.forename: Guang-hui
authors.initials: GH
authors.lastname: Du
authors.forename: Zhong-hua
authors.initials: ZH
authors.lastname: Liu
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001713:Biphenyl Compounds / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D000077143:Docetaxel; D004357:Drug Synergism; D006801:Humans; D008297:Male; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000378:metabolism; D009596:Nitrophenols / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology*; D043823:Taxoids / Q000494:pharmacology*; D051020:bcl-X Protein / Q000378:metabolism
chemical_list: C501332:ABT-737; C494811:BCL2L1 protein, human; D001713:Biphenyl Compounds; C579095:MCL1 protein, human; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009596:Nitrophenols; D010879:Piperazines; D019253:Proto-Oncogene Proteins c-bcl-2; D013449:Sulfonamides; D043823:Taxoids; D051020:bcl-X Protein; D000077143:Docetaxel; C505407:CASP3 protein, human; D053148:Caspase 3