Enhancement of reversing effect of cyclosporin A on vincristine resistance by anti-P-glycoprotein monoclonal antibody MRK-16.
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.
Naito
M
M
Institute of Applied Microbiology, University of Tokyo.
Tsuge
H
H
Kuroko
C
C
Tomida
A
A
Tsuruo
T
T
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*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000911:Antibodies, Monoclonal; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D014750:Vincristine; D016572:Cyclosporine