title: Reversal of multidrug resistance in Chinese hamster ovary cells by the immunosuppressive agent rapamycin.
abstract: 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.
authors.affiliation: Abteilung Biophysikalische Chemie, Medizinische Hochschule Hannover, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Hoof
authors.forename: A
authors.initials: A
authors.lastname: Demmer
authors.forename: U
authors.initials: U
authors.lastname: Christians
authors.forename: B
authors.initials: B
authors.lastname: Tümmler
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000345:Affinity Labels; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D016466:CHO Cells; D002352:Carrier Proteins / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D016572:Cyclosporine / Q000494:pharmacology; D003630:Daunorubicin / Q000494:pharmacology; D004351:Drug Resistance; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008562:Membrane Glycoproteins / Q000378:metabolism; D011090:Polyenes / Q000494:pharmacology*; D020123:Sirolimus; D013388:Succinimides; D016559:Tacrolimus / Q000494:pharmacology; D014748:Vinca Alkaloids / Q000494:pharmacology
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000345:Affinity Labels; D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D002352:Carrier Proteins; D007166:Immunosuppressive Agents; D008562:Membrane Glycoproteins; D011090:Polyenes; D013388:Succinimides; D014748:Vinca Alkaloids; C022581:Bolton-Hunter reagent; D016572:Cyclosporine; D020123:Sirolimus; D016559:Tacrolimus; D003630:Daunorubicin