Modulation of Multidrug Resistance by SDZ PSC 833 in Leukemic and Solid‐tumor‐bearing Mouse Models

摘要: P-Glycoprotein inhibitors, including the nonimmunosuppressive cyclosporin D analog SDZ PSC 833 (PSC 833), have been developed to circumvent multidrug resistance. In present study, potential of in reversing resistance was evaluated various systemic treatment models with leukemic and solid-tumor-bearing mice. Having a relatively wide therapeutic window daily p.o. doses from 12.5 75 mg/kg, significantly improved antileukemic activity anticancer drugs adriamycin (ADM), vincristine (VCR) etoposide (VP-16) given i.p. or i.v. against i.p.-inoculated vincristine-resistant P388 tumor (P388/VCR). combination i.p.-injected optimal schedule dosage induced apparent cures some mice, whereas no were obtained A/anticancer drug combinations. combined i.v.-injected highly active, but not curative, P388/VCR parental tumors (maximum T/C>175%). intravenous ADM showed prominent anti-solid-tumor s.c.-inoculated colon adenocarcinoma 26 human colorectal HCT-15. Against 26, 833/ADM combinations cure two three six inhibited growth maximum percent inhibitions 83 73% early advanced stages HCT-15 models, respectively. The study demonstrated that is active potentiating antitumor systemically administered ADM, VCR VP-16 four murine dose range 12.5–100 mg/kg.