Potentiation of the reversal activity of SDZ PSC833 on multi-drug resistance by an anti-p-glycoprotein monoclonal antibody MRK-16
✍ Scribed by Mikihiko Naito; Toru Watanabe; Harumi Tsuge; Tomoko Koyama; Tomoko Oh-Hara; Takashi Tsuruo
- Publisher
- John Wiley and Sons
- Year
- 1996
- Tongue
- French
- Weight
- 564 KB
- Volume
- 67
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
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 MAC. enhanced MDR reversal activity of cyclosporin A (CsA) through inhibition of P-glycoprotein-mediated CrA 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-I6 combined with CsA, MRK-I6 enhanced the effect of a sub-optimum dose of PSC833 on vincristine accumulation in MDR cells. However. MRK-I6 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-I6 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. o I996 Wiley-Liss, Inc.
Drug resistance is a major obstacle to successful cancer chemotherapy. When tumor cells acquire resistance against a certain chemotherapeutic drug, they often show crossresistance to a variety of anti-tumor drugs. The mechanism of multi-drug resistance (MDR) has been well studied, and P-glycoprotein, an efflux pump for hydrophobic anti-tumor drugs, plays a key role in MDR