R-dl-型维拉帕米调低KBv200肿瘤细胞对长春新碱和多柔比星的多药抗药性<英文>  

R-dl-Verapamil downmodulates multidrug resistance of KBv200 cells to vincristine and doxorubicin

作　　者：方刚[1] 杨玉龙[1] 黎介寿[1] 张祖暄[1] 

机构地区：[1]南京大学医学院,南京中国210093

出　　处：《中国药理学报》1999年第7期647-650,共4页Acta Pharmacologica Sinica

摘　　要：目的:研究R-型维拉帕米对多药耐药的降低作用及其急性动物毒性,并与消旋维拉帕米的相应结果作比较。方法:细胞毒性的测定用MTT法;细胞内多柔比星积累的测定用萤光分光光度计法。急性毒性试验用BALB/c小鼠腹腔注射法。结果:R-型维拉帕米部分调低KBv200细胞对长春新碱和多柔比星的耐药性,其调低效应与作用浓度和作用时间有关。1.25μmol·L^(-1)的R-型维拉帕米与长春新碱对细胞作用24h,能够显著增加KBv200细胞对长春新碱的敏感性。在增敏和增加细胞内多柔比星累积方面,R-型维拉帕米与消旋维拉帕米效果一样,但R-型维拉帕米的急性动物毒性明显低于消旋维拉帕米。结论:R-型维拉帕米1.25μmol·L^(-1)提高耐药肿瘤细胞对长春新碱和多柔比星的敏感性,增加对长春新碱敏感性所需的药物作用时间可缩短至24h。AIM: To study the attenuation of multidrug resistance (MDR) by R-dl-verapamil (R-Ver) and the acute animal toxicity of R-Ver, and to compare these results of R-Ver with the results of dl-verapamil (Ver). METHODS: Cytotoxicity was determined by tetrazolium (MTT) assay. Cellular accumulation of doxorubicin ( Dox) was measured by fluorescence spectrophotometry. Acute animal toxicity was tested by ip drug administration in BALB/c mice. RESULTS: R-Ver attenuated MDR of KBv200 cells to vincristine (VCR) and Dox. This attenuation ability was dose-related, and was also dependent on drug exposure time. R-Ver 1.25μmol·L-1 increased the sensitivity of KBv200 cells to VCR ( P < 0.01) with a 24-h period of drug exposure. R-Ver downmodulated MDR and increased cellular Dox accumulation of KBv200 cells as effectively as Ver, but possessed lower acute toxicity in BALB/c mice. While LD50 of Ver was 60 (49 - 73) mg·kg-1, LD50 of R-Ver was 166 (137 - 202) mg·kg-1. CONCLUSION: R-Ver downmodulated the MDR to VCR and Dox at 1.25 μmol·L-1, and this effect on VCR can be realized with drug exposure duration of 24 h.

关 键 词：维拉帕米 长春新碱 多柔比星 多药耐药性 

分 类 号：R730.5[医药卫生—肿瘤]