CHEMOSENSITIZING EFFECT OF VERAPAMIL ON SWISS-3T3 CELLS TRANSFECTED WITH HUMAN MDR1 GENE

To further understand the characteristics of drug resistance reversal of verapamil,the relationship between the level of doxorubicin resistance and the magnitude of modulation by verapamil was examined in multidrug resistant Swiss-3T3 cells transfected with human MDR1 gene,In independently isolated transfectants doxorubicin cytotoxicity decreased markedly compared with parent cells. Potentiation of doxorubicin toxicity by a noncytotoxic concentration of 3μmol·L^-1 of verapamil was much greater in transfectants than in parent cells,while the magnitude of reversal was inversely dependent on the level of resistance.Southern blot hybridization indicated the MDR1 cDNA integration in genomics of each transfectant.Defect in cellular accumulation of doxorubicin was restored by verapamil in transfected cells.The saturation of active drug transport that may involve the magnitude changes of potentiation by verapamil,and the mode of interaction between P-glycoprotein and drugs,were discussed.