Reversal of multidrug resistance in Chinese hamster ovary cells by the immunosuppressive agent rapamycin.

The ability of cyclosporin A, FK506, and rapamycin to overcome multidrug resistance was investigated in Chinese hamster ovary cells in vitro by growth inhibition experiments. 1-30 microM of immunosuppressant sensitized drug-resistant cells and their drug-sensitive parents in a dose-dependent manner to adriamycin (2-2000-fold), colchicine (2-260-fold), and vinblastine (2-120-fold). The multidrug resistance-reversing activity increased in the order rapamycin < FK506 < cyclosporin A, irrespective of whether the resistant cells overexpressed hamster or human P-glycoprotein. The interaction of the three macrolides with P-glycoprotein was characterized by their ability to competitively inhibit the photoaffinity labelling of plasma membranes of resistant CHRB30 cells by iodomycin. The three immunosuppressants bound with high affinity to P-glycoprotein.