Potentiation of the reversal activity of SDZ PSC833 on multi-drug resistance by an anti-p-glycoprotein monoclonal antibody MRK-16
Mikihiko Naito
Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo, Japan
Search for more papers by this authorToru Watanabe
Tsukuba Research Institute, Sandoz Pharmaceuticals, Ltd., Ohkubo, Tsukuba, Ibaragi, Japan
Search for more papers by this authorHarumi Tsuge
Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo, Japan
Search for more papers by this authorTomoko Koyama
Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo, Japan
Search for more papers by this authorTomoko Oh-Hara
Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo, Japan
Search for more papers by this authorCorresponding Author
Takashi Tsuruo
Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo, Japan
Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo, Japan
Institute of Molecular and Cellular Biosciences, The University of Tokyo, Yayoi, Bunkyo-ku, Tokyo 113, JapanSearch for more papers by this authorMikihiko Naito
Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo, Japan
Search for more papers by this authorToru Watanabe
Tsukuba Research Institute, Sandoz Pharmaceuticals, Ltd., Ohkubo, Tsukuba, Ibaragi, Japan
Search for more papers by this authorHarumi Tsuge
Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo, Japan
Search for more papers by this authorTomoko Koyama
Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo, Japan
Search for more papers by this authorTomoko Oh-Hara
Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo, Japan
Search for more papers by this authorCorresponding Author
Takashi Tsuruo
Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo, Japan
Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo, Japan
Institute of Molecular and Cellular Biosciences, The University of Tokyo, Yayoi, Bunkyo-ku, Tokyo 113, JapanSearch for more papers by this authorAbstract
SDZ PSC833 (PSC833), an analogue of cyclosporines, is one of the most potent modulators of multi-drug resistance (MDR). We previously reported that MRK-16, an anti-P-glycoprotein MAb, enhanced MDR reversal activity of cyclosporin A (CsA) through inhibition of P-glycoprotein-mediated CsA transport. We have examined here whether MRK-16 can enhance MDR reversal activity of PSC833. We found that MRK-16 potentiated the MDR reversal activity of PSC833, and of CsA, in MDR sublines of human myelocytic leukemia K562 and human ovarian cancer A2780 cells. Like MRK-16 combined with CsA, MRK-16 enhanced the effect of a sub-optimum dose of PSC833 on vincristine accumulation in MDR cells. However, MRK-16 could not increase cellular accumulation of PSC833 in MDR tumor cells, yet it could increase cellular accumulation of CsA. P-glycoprotein could not transport PSC833 but could transport CsA. Our results indicate that MRK-16 potentiates the MDR reversal activity of both PSC833 and CsA, yet also suggest that the molecular mechanism of the potentiation differs between the two substances. © 1996 Wiley-Liss, Inc.
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