In vivo reversal of doxorubicin resistance by a new tiapamil analog Ro11-2933.

摘要: The effectiveness of a calcium antagonist analog Ro11-2933 to modulate doxorubicin (DOX) response in DOX-sensitive (WT) and -resistant (DOXr, 200-fold) cell lines was investigated compared verapamil (VP) vitro vivo rats bearing mammary carcinoma using equivalent nontoxic doses. In exposure concentration (2 microM) normalizes the DOX accumulation defect observed DOXr cells, increases DOX-induced DNA single-strand breaks effectively sensitizes cells DOX. Ten microM VP required obtain an effect that seen with 2 Ro11-2933. Intravenous administration at 5 mg/kg rat tumors has no significant therapeutic on tumor growth (P > .5), whereas it found effective inhibiting WT .1). Combination inhibits as alone. less than results were not statistically from treatment alone .5). Our data demonstrate is well tolerated after i.v. modulator resistance solid model.