ACTIVITY OF DIFFERENT REVERTANT AGENTS ON MULTIDRUG-RESISTANCE - IN-VITRO EVALUATION OF THEIR COMBINATION

The revertant activity of different compounds has been assayed on a mu ltidrug-resistant human breast-cancer cell line (MCF 7/Dx). The calciu m-channel blocker nicardipine showed the higher revertant ability when compared to cefoperazone or cyclosporin A at concentrations close to the pharmacological range. Interestingly, nicardipine was able to incr ease the revertant activities of both cefoperazone and cyclosporin A, but these latter were not able to enhance each other over a plateau. H owever, a limit of about 70% of growth inhibition of the line cultured in the presence of 60 muM doxorubicin seems to be insuperable at the concentrations employed. The combination of the three drugs brings the concentrations of drugs to the point at which the maximum possible in hibition is reached in the pharmacological range, but the complete rev ersion of chemoresistance is not reached when the doxorubicin is added at the concentration capable of reducing the cell proliferation by 50 %.