Modulation of multidrug resistance by SDZ PSC 833 in leukemic and solid-tumor-bearing mouse models

Japanese Journal of Cancer Research : Gann
T WatanabeT Tsuruo

Abstract

P-Glycoprotein inhibitors, including the nonimmunosuppressive cyclosporin D analog SDZ PSC 833 (PSC 833), have been developed to circumvent multidrug resistance. In the present study, the potential of PSC 833 in reversing multidrug resistance was evaluated in various systemic treatment models with leukemic and solid-tumor-bearing mice. Having a relatively wide therapeutic window of daily p.o. doses from 12.5 to 75 mg/kg, PSC 833 significantly improved the antileukemic activity of the anticancer drugs adriamycin (ADM), vincristine (VCR) and etoposide (VP-16) given i.p. or i.v. against i.p.-inoculated vincristine-resistant P388 tumor (P388/VCR). PSC 833 in combination with i.p.-injected anticancer drugs in optimal schedule and dosage induced apparent cures in some leukemic mice, whereas no cures were obtained with the cyclosporin A/anticancer drug combinations. PSC 833 combined with i.v.-injected anticancer drugs was highly active, but not curative, against P388/VCR and parental P388 tumors (maximum T/C>175%) PSC 833 in combination with intravenous treatment with ADM showed prominent anti-solid-tumor activity against s.c.-inoculated colon adenocarcinoma 26 and human colorectal adenocarcinoma HCT-15. Against colon adenocarcinoma 2...Continue Reading

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Citations

Feb 28, 2001·Nature Biotechnology
Oct 3, 1999·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·E BovenO van Tellingen
Oct 6, 1997·British Journal of Pharmacology·T WatanabeD Cohen
Jul 5, 2005·Expert Opinion on Investigational Drugs·F Loor
Apr 9, 1998·Critical Reviews in Clinical Laboratory Sciences·W van de VrieA M Eggermont
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Jul 16, 2005·Pediatric Hematology and Oncology·Steven W WarmannJörg Fuchs
Oct 18, 2000·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·R Krishna, L D Mayer

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