环孢素A对白血病耐药细胞化疗药物敏感性的研究.pdfVIP

肿瘤基础与临床2008年2月第21卷第1期 · l3- 环孢素A对白血病耐药细胞化疗药物敏感性的研究 刘 玲 。范高路 (1．河南科技大学医学院，河南 洛阳471003；2．洛阳市第三人民医院，河南 洛阳471002) 摘要：目的 研究环孢素A对K562／DOX细胞多药耐药的逆转作用。方法 用流式细胞仪和 MTT法观察了CsA对 K562／DOX细 胞P一糖蛋白的抑制作用及对阿霉素(doxorubicin，DOX)、长春新碱(vincristine，VCR)耐药的逆转作用。结果 CsA能剂量相关性 地增加K562／DOX细胞内罗丹明123(rhodamine123，Rh123)的累积，明显抑制P—gP介导的Rh123外排，显著增强 DOX、VCR的细 胞毒作用，增加VCR诱导的细胞凋亡和G，／M期细胞百分率。结论 CsA能显著抑制P—gp的外排功能，逆转 K562／DOX细胞的多 药耐药性。 关键词：环孢素A；P一糖蛋白；多药耐药；凋亡 中图分类号：R733．7；R730．53 文献标识码：A 文章编号：1673—5412(2008)01—0013一O4 The Inhibition Effects of Cyclosporin A on Leukemia Cells of Drug—Resistance by Cytotoxic Drugs Liu Ling，Fan Gaolu (Department of Pharmacology，Henan University of Science and Technology，Luoyang 47 1 003，China) Abstract：0bjective To study the reversal effects of multidrug resistance by CsA in doxorubicin—resistant human myelogenous leukemia (K562／DOX)cells．Methods The effects of CsA on P—gP function and resistance to doxorubicin(DOX)／vincristine(VCR)in K562／DOX cells were observed by using flow cytometric technology and MTT assay．Results CsA increased intracellular accumulation of Rht23 in K562／DOX cells in a concentration—related manner and significantly inhibited the eff!ux of rhodamine123(Rh123)from the cells，the doxo— rubiein／vincristine—induced cytotoxicity was significantly potentiated by CsA．Meanwhile，it increased the apoptosis and the percent of cells in G2／M phase induced by VCR in K562／DOX cells．Conclusions The reversed effects of CsA on muhidrug resistance in K562／DOX cells were associated with its inhibitory effects on P—gP efflux function． Key words：CsA；P—glycoprotein；multidrug resistance；apoptosis 多药耐药性(multidrug resistance，MDR)的形成是 素为浙江海正药业股份有限公司产品。硫酸长春新碱 肿瘤化疗失败的重要原因，肿瘤细胞上P一糖蛋白(P— 为上海华联制药有限公司产品。仪器：XD一101倒置显 glycoprotein，P—gP)的高度表达及其诱导的药物外排是