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

摘要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.

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分类号 R1
栏目名称 ORIGINAL ARTICLE
DOI 10.3760/cma.j.issn.0366-6999.2011.23.032
发布时间 2012-01-12
基金项目
the Administration of Traditional Chinese Medicine of Zhejiang Province,China
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中华医学杂志(英文版)

中华医学杂志(英文版)

2011年124卷23期

4018-4021页

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