Increased ABCB1 Expression in TP-110-Resistant RPMI-8226 Cells
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概要
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TP-110, a novel proteasome inhibitor, has been found to possess potent growth inhibition in human multiple myeloma cells. To enhance its therapeutic effects, we established TP-110-resistant RPMI-8226 (RPMI-8226/TP-110) cells and elucidated their resistance mechanisms. The IC50 value for TP-110 cytotoxicity in the RPMI-8226/TP-110 cells was about 10-fold higher than that of the parental sensitive cells. The RPMI-8226/TP-110 cells exhibited distinct drug resistance to other proteasome inhibitors. Furthermore, they showed high cross-resistance to the cytotoxic effects of doxorubicin, etoposide, taxol, and vincristine. P-glycoprotein (MDR1), encoded by ABCB1, was elevated in the RPMI-8226/TP-110 cells, and the MDR1 inhibitor verapamil overcame their resistance to TP-110. The results of DNA microarray and RT-PCR suggested that the expression of ABCB1 is significantly elevated in RPMI-8226/TP-110 cells. This indicates that resistance in RPMI-8226/TP-110 cells is involved in the expression of P-glycoprotein, a drug-efflux pump.
- 2010-09-23
著者
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ISHIZUKA Masaaki
Institute for Chemotherapy
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MOMOSE Isao
Institute of Microbial Chemistry
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Imoto M
Department Of Applied Chemistry Faculty Of Science And Technology Keio University
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Ikeda D
Numazu Bio-medical Research Institute Microbial Chemistry Research Foundation
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Ikeda Daishiro
Numazu Bio-medical Research Institute Microbial Chemistry Research Center
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Iijima Masatomi
Numazu Bio-medical Research Institute Microbial Chemistry Research Center
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Momose Isao
Numazu Bio-medical Research Institute Microbial Chemistry Research Center
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