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.Conclusion These data suggested that inhibition of Bcl-2 expression combined with epirubicin may be an attractive therapeutic strategy in hormone-refractory prostate cancer.