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Potentiation of the reversal activity of SDZ PSC833 on multi‐drug resistance by an anti‐p‐glycoprotein monoclonal antibody MRK‐16
Author(s) -
Naito Mikihiko,
Watanabe Toru,
Tsuge Harumi,
Koyama Tomoko,
OhHara Tomoko,
Tsuruo Takashi
Publication year - 1996
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19960729)67:3<435::aid-ijc20>3.0.co;2-5
Subject(s) - p glycoprotein , multiple drug resistance , pharmacology , monoclonal antibody , drug resistance , chemistry , biology , antibody , immunology , genetics
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.