Reversal of multidrug resistance by RU 486.
basic_science · Level V
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Abstract
P-Glycoproteins represent a family of drug efflux proteins that convey multidrug resistance to cells in which they are expressed. This phenomenon can lower the efficacy of drugs used in chemotherapy. The steroid progesterone has been shown to bind P-glycoproteins and inhibit their drug efflux. We report that the antiprogestin RU 486 can reverse multidrug resistance in cells overexpressing the mouse mdr1 gene. Using flow cytometry to measure inhibition of P-glycoprotein-dependent efflux 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.
Medical subject headings
- Antineoplastic Agents
- Carrier Proteins
- Drug Resistance
- Membrane Glycoproteins
- Mifepristone