title: Enhancement of reversing effect of cyclosporin A on vincristine resistance by anti-P-glycoprotein monoclonal antibody MRK-16.
abstract: The synergistic effect of MRK-16, a monoclonal antibody against P-glycoprotein, and cyclosporin A (CsA) on the modulation of vincristine resistance was studied by isobologram analysis in three different, highly multidrug-resistant tumor cells. In all cell lines, the synergistic effect was demonstrated at various concentrations of MRK-16 and CsA. While MRK-16 alone did not enhance the sensitivity of the moderately resistant KB-8-5 cells to vincristine, it increased two-fold the reversing effect of cyclosporin A at 1 microM, an achievable blood concentration. Since MRK-16 alone showed therapeutic effects against multidrug-resistant tumors, the combined use of MRK-16, CsA and antitumor agents should provide therapeutic benefits for the treatment of resistant tumors.
authors.affiliation: Institute of Applied Microbiology, University of Tokyo.
authors.forename: M
authors.initials: M
authors.lastname: Naito
authors.forename: H
authors.initials: H
authors.lastname: Tsuge
authors.forename: C
authors.initials: C
authors.lastname: Kuroko
authors.forename: A
authors.initials: A
authors.lastname: Tomida
authors.forename: T
authors.initials: T
authors.lastname: Tsuruo
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000911:Antibodies, Monoclonal / Q000276:immunology*; D002352:Carrier Proteins / Q000276:immunology*; D016572:Cyclosporine / Q000494:pharmacology*; D004351:Drug Resistance; D006801:Humans; D007624:KB Cells; D008562:Membrane Glycoproteins / Q000276:immunology*; D014750:Vincristine / Q000494:pharmacology*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000911:Antibodies, Monoclonal; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D014750:Vincristine; D016572:Cyclosporine