Inhibition of Bcl-2 enhances the efficacy of epirubicin chemotherapy in PC-3 prostate cancer cells

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 MIT 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. Chin Med J 2011;124(23):4018-4021