FK-506 (fujimycin) reverses the multidrug resistance of tumor cells in vitro.
Cyclosporin A (CsA) and FK-506 have similar immunosuppressive activity profiles and cyclophilin-like intracellular targets. Since CsA can reverse the multidrug resistance of tumor cells showing P-glycoprotein-mediated drug efflux, the possible resistance-modulating activity of FK-506 was evaluated in vitro with multidrug-resistant P388 cells and their sensitive parental controls. Higher concentrations of FK-506 than CsA were needed to achieve a similar degree of chemosensitization, suggesting that FK-506 might interact less efficiently than CsA with the P-glycoprotein expressed in multidrug-resistant tumor cells. However, FK-506 was active on a broader range of concentrations than CsA, particularly because of direct cytostatic effects of CsA which appeared at concentrations only slightly higher than those required to show a significant resistance-modulating activity.
Pourtier-Manzanedo
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Laboratoire d'Immunologie, Université Louis Pasteur Strasbourg, Illkirch, France.
Boesch
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D
Loor
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F
D000638:Amiodarone / Q000494:pharmacology; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D016572:Cyclosporine / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology; D004351:Drug Resistance; D007941:Leukemia P388 / Q000188:drug therapy; D016559:Tacrolimus / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects*; D014700:Verapamil / Q000494:pharmacology; D014750:Vincristine / Q000494:pharmacology
D000903:Antibiotics, Antineoplastic; D014750:Vincristine; D004317:Doxorubicin; D016572:Cyclosporine; D014700:Verapamil; D000638:Amiodarone; D016559:Tacrolimus