Immunosuppressants FK506 and rapamycin function as reversal agents of the multidrug resistance phenotype.

摘要: The multidrug-resistant (MDR) phenotype is characterized in vitro by the resistance displayed cell lines to a broad spectrum of natural product cytotoxic agents. This high level cross-resistance due increased expression membrane glycoprotein termed P- glycoprotein. Encoded humans mdr1 gene, P-glycoprotein functions as an energy-dependent efflux pump these In this report, we demonstrate that newly immunosuppressant FK506 and its structural analogue, rapamycin, are capable functioning MDR reversal rapamycin increase both intracellular, drug (daunomycin) accumulation, cytotoxicity chemotherapeutic agents cells. accumulation observed at concentrations 1,000-fold greater than required for inhibit T-lymphocyte activation similar those shown be effective other such cyclosporine A (CsA) verapamil. effect or on intracellular daunomycin additive. supported ability directly compete binding photoaffinity analogue 125I-iodoaryl azidoprazosin data represent new class structurally distinct molecules can function suggest previously unidentified, potential clinical role compounds.