盐酸千金藤碱逆转MCF-7/ADR细胞多药耐药性的作用及其机制

摘要

Objective To investigate the reversal effect of cepharanthine hydrochloride(CH) on multidrug resistance(MDR) of drug-resistant cell line of human breast epithelial carcimoma(MCF-7/∧DR),and to explore its mechanism. Methods MTT assay was used to detect cytotoxicity and MDR reversal activity of CH in MCF-7/ADR cell line. Immunohistochemistry(IHC) technique was used to show the intracellular expression of glutathione S-transferases pi(GST-π). The catalytic activity of DNA Topoisomerase(Topo Ⅱ ) was assessed by the ∧TP-dependent relaxation of supercoild pBR322 DN∧. Results CH could enhance sensitivity of MCF-7/∧DR cells to anti-tumor drugs. A 13.5 fold reversed effect of resistance was achieved in vitro. However,CH had few effects on drug-sensitive MCF-7 cells. After treatment of CH under the concentration of 4μmol/L, the level of higher expression of GST-π was decreased and the activity of DNA Topo Ⅱ was increased in MCF-7/ADR cell line,but no changes was found in MCF-7 cells. Conclusion CH is able to effectively reverse drug resistance and its mechanism is probably related to reducing the expression of GST-π and enhancing the activity of DNA Topo Ⅱ in MDR tumor cells.%目的 研究盐酸千金藤碱(CH)对人乳腺上皮细胞癌耐药细胞株MCF-7/阿霉素(ADR)多药耐药性的体外逆转作用,并探讨其逆转机制.方法 用四甲基偶氮唑盐(MTT)法检测CH对多药耐药肿瘤细胞MCF-7/ADR的耐药逆转活性;免疫组织化学法检测细胞内谷胱甘肽硫转移酶π(GST-π)的表达;通过对超螺旋PBR322 DNA的解旋能力检测拓扑异构酶Ⅱ(TopoⅡ)的活性.结果 CH在无细胞毒浓度下具有逆转MCF-7/ADR细胞耐药性的作用,逆转倍数为13.5倍,但对敏感株MCF-7细胞的抗癌药物敏感性基本无影响.CH 4 μmol/L 使MCF-7/ADR细胞中过度表达的GST-π的表达水平下降及DNA TopoⅡ的催化活性提高,但对敏感株MCF-7细胞无影响.结论 CH具有逆转多药耐药性的作用,其机制可能与降低GST-π的表达及提高DNA TopoⅡ的活性有关.