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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。
OBJECTIVE: To study the reduction of multidrug resistance in R-type verapamil and its acute toxicity to animals and compare it with the corresponding results of racemic verapamil. Methods: MTT assay was used for the determination of cytotoxicity; fluorescence spectrophotometry was used for the determination of intracellular doxorubicin accumulation. Acute toxicity test was performed by intraperitoneal injection of BALB/c mice. RESULTS: R-type verapamil partially reduced the resistance of KBv200 cells to vincristine and doxorubicin, and its down-regulation effect was related to the concentration and duration of action. 1.25μmol·L -1 R-type verapamil and vincristine on cells for 24h, can significantly increase the sensitivity of KBv200 cells to vincristine. In terms of sensitization and increase of intracellular doxorubicin accumulation, R-type verapamil has the same effect as racemic verapamil, but R-type verapamil has a significantly lower acute toxicity than racemic verapamil. Meter. CONCLUSION: R-type verapamil 1.25 μmol·L -1 increases the sensitivity of drug-resistant tumor cells to vincristine and doxorubicin, and increases the drug-action time required for the sensitivity to vincristine. Reduced to 24h.