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  

Reversal of multidrug resistance in MCF-7/ADR cells by cepharanthine hydrochloride and its mechanism

作　　者：夏薇 王宁 王庆端 

机构地区：[1]河南省医药科学研究院药化室,郑州450052

出　　处：《重庆医学》2011年第1期14-16,19,共4页Chongqing medicine

摘　　要：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。CH4μmol/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。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/ADR）,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（TopoⅡ） was assessed by the ATP-dependent relaxation of supercoild pBR322 DNA.Results CH could enhance sensitivity of MCF-7/ADR 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 TopoⅡwas 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 TopoⅡ in MDR tumor cells.

关 键 词：乳腺肿瘤 抗药性 多药 谷胱甘肽转移酶 DNA拓扑异构酶 盐酸千金藤碱 

分 类 号：R285.5[医药卫生—中药学]