title: Inhibition of Bcl-2 enhances the efficacy of epirubicin chemotherapy in PC-3 prostate cancer cells.
abstract: BACKGROUND
  Overexpression of Bcl-2 protein in cancer cells can inhibit programmed cell death and engender chemoresistance. Bcl-2 antisense oligonucleotide (G3139) has shown its antitumor effects enhanced in preclinical models when combined with taxol-based chemotherapy. This study aimed to investigate the efficacy of G3139 combined with epirubicin in the androgen-independent prostate cancer.
  
  
  METHODS
  PC3 prostate cancer cell line was cultured and treated with epirubicin and Bcl-2 antisense oligonucleotide alone or in combination. The effects of therapeutic agents on cells were determined by the MTT assay. Expression of Bcl-2 mRNA and protein was documented by RT-PCR and Western blotting. Apoptosis induction was confirmed by flow cytometric analysis.
  
  
  RESULTS
  Bcl-2 antisense oligonucleotide alone produced no cytotoxic effects and the combination of Bcl-2 antisense oligonucleotide with epirubicin sensitized PC-3 cells to the killing effects of chemotherapy. A marked down-regulation of Bcl-2 mRNA and protein was observed after antisense and epirubicin cotreatment. A statistically significantly higher fraction of apoptotic cells was detected by flow-cytometric analysis after epirubicin treatment with prior antisense Bcl-2 transfenction, as compared with mono antisense Bcl-2 or epirubicin treatment.
  
  
  CONCLUSIONS
  These data suggested that inhibition of Bcl-2 expression combined with epirubicin may be an attractive therapeutic strategy in hormone-refractory prostate cancer.
authors.affiliation: Department of Urology, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, China.
authors.forename: Hai
authors.initials: H
authors.lastname: Jiang
authors.forename: Dan
authors.initials: D
authors.lastname: Xia
authors.forename: Ling-Jiao
authors.initials: LJ
authors.lastname: Wu
authors.forename: Zhao-Dian
authors.initials: ZD
authors.lastname: Chen
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D015251:Epirubicin / Q000494:pharmacology*; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D016376:Oligonucleotides, Antisense / Q000235:genetics; D011471:Prostatic Neoplasms / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D016376:Oligonucleotides, Antisense; D019253:Proto-Oncogene Proteins c-bcl-2; D015251:Epirubicin