REVERSAL OF MULTIDRUG-RESISTANCE BY RU-486

P-Glycoproteins represent a family of drug efflux proteins that convey multidrug resistance to cells in which they are expressed. This pheno me non can lower the efficacy of drugs used in chemotherapy. The stero id progesterone has been shown to bind P-glycoproteins and inhibit the ir drug efflux. We report that the antiprogestin RU 486 can reverse mu ltidrug resistance in cells overexpressing the mouse mdr1 gene. Using flow cytometry to measure inhibition of P-glycoprotein-dependent efflu x of rhodamine 123, RU 486 was found to be considerably more effective than progesterone and one-half as effective as verapamil. The results suggest a valuable new use for RU 486.