论文部分内容阅读
为进一步了解维拉帕米对抗药性逆转作用的待征，在人ＭＤＲ１基因转染的Ｓｗｉｓｓ－３Ｔ３多药抗药性细胞，观察了维拉帕米逆转幅度与阿霉素抗性水平的关系。各个转染细胞与母细胞相比，阿霉素毒性明显降低。非毒性浓度（３Ｕｍｏｌ·Ｌ－１）的维拉帕米对阿霉素毒性的增强作用，在转染细胞均高于母细胞，但逆转幅度与抗性水平成反比。Ｓｏｕｔｈｅｒｎ杂交显示，转染细胞基因组中有ＭＤＲ１ｃＤＮＡ整合。转染细胞的阿霉素蓄积障碍可被维拉帕米纠正。讨论了药物主动转运的饱和现象在维拉帕米增强效应中的作用，以及Ｐ－糖蛋白与药物相互作用的方式。
To further understand the reversal effect of verapamil on drug resistance, the relationship between verapamil reversal amplitude and doxorubicin resistance was observed in human MDR1 gene-transfected Swiss-3T3 multidrug resistant cells. Adriamycin toxicity was significantly lower in all transfected cells than in parental cells. Verapamil at a non-toxic concentration (3 Umol·L -1) enhanced the doxorubicin toxicity in transfected cells at a higher level than that of blast cells, but the magnitude of reversal was inversely proportional to the level of resistance. Southern blotting showed that there was MDR1 cDNA integration in the transfected cell genome. Doxorubicin accumulation in transfected cells can be corrected by verapamil. The role of saturation of drug active transport in the potentiation of verapamil and the way in which P-glycoprotein interacts with drugs are discussed.