Journal article
In vivo reversal of doxorubicin resistance by a new tiapamil analog Ro11-2933
The Journal of pharmacology and experimental therapeutics, Vol.264(3), pp.1299-1304
1993
DOI: 10.1016/S0022-3565(25)10145-6
PMID: 8450465
Abstract
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 and compared to verapamil (VP) in vitro and in vivo in rats bearing mammary carcinoma using equivalent nontoxic doses. In vitro exposure to a nontoxic concentration of Ro11-2933 (2 microM) normalizes the DOX accumulation defect observed in DOXr cells, increases DOX-induced DNA single-strand breaks and effectively sensitizes DOXr cells to DOX. Ten microM VP was required to obtain an effect equivalent to that seen with 2 microM Ro11-2933. Intravenous administration of DOX at 5 mg/kg to the rat bearing the DOXr tumors has no significant therapeutic effect on tumor growth (P > .5), whereas it was found effective in inhibiting the growth of WT tumors (P < .05). Ro11-2933 or VP administered alone has no significant effect on tumor growth as compared to a saline-treated group (P > .1). Combination of Ro11-2933 with DOX effectively inhibits DOXr tumor growth as compared to DOX alone. Combination of DOX with VP was found less effective than Ro11-2933 and the results were not statistically significant from DOX treatment alone (P > .5). Our data demonstrate that Ro11-2933 is well tolerated after i.v. administration and an effective modulator of DOX resistance in a solid tumor model.
Details
- Title: Subtitle
- In vivo reversal of doxorubicin resistance by a new tiapamil analog Ro11-2933
- Creators
- Moulay A Alaoui-Jamali - McGill UniversityRobyn L Schecter - McGill UniversityYoucef M Rustum - McGill UniversityMaria G Centurioni - McGill UniversityShirley Lehnert - McGill UniversityGerald Batist - McGill University
- Resource Type
- Journal article
- Publication Details
- The Journal of pharmacology and experimental therapeutics, Vol.264(3), pp.1299-1304
- Publisher
- American Society for Pharmacology and Experimental Therapeutics
- DOI
- 10.1016/S0022-3565(25)10145-6
- PMID
- 8450465
- ISSN
- 0022-3565
- eISSN
- 1521-0103
- Language
- English
- Date published
- 1993
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984360049102771
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