Abstract
A novel multidrug resistance modulator, RS-33295-198, circumvented drug resistance in human, mouse, and Chinese hamster cell lines overexpressing P-glycoprotein. It enhanced the antiproliferative activity of doxorubicin, vincristine, etoposide, and paclitaxel and increased doxorubicin retention in multidrug-resistant hamster CHRC5 cells. RS-33295-198 modulated doxorubicin resistance in a murine P388/ADR leukemia model when administered ip via continuous minipump delivery, ip by bolus injection, and orally; it also improved the efficacy of vincristine toward P388/VCR leukemia when given ip or po. RS-33295-198 showed weak activity in enhancing doxorubicin efficacy against a multidrug-resistant human sarcoma xenograft.
MeSH terms
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ATP Binding Cassette Transporter, Subfamily B, Member 1 / drug effects
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ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism*
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Animals
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Antineoplastic Agents / toxicity*
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Cell Division / drug effects
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Cell Line
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Cricetinae
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Cricetulus
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Dibenzocycloheptenes / pharmacology*
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Dibenzocycloheptenes / therapeutic use
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Doxorubicin / metabolism
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Doxorubicin / toxicity
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Drug Resistance, Multiple / physiology*
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Drug Synergism
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Etoposide / toxicity
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Leukemia P388 / drug therapy*
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Mice
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Mice, Nude
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Paclitaxel / toxicity
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Quinolines / pharmacology*
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Quinolines / therapeutic use
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Sarcoma / drug therapy
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Transplantation, Heterologous
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Vincristine / therapeutic use
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Vincristine / toxicity
Substances
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ATP Binding Cassette Transporter, Subfamily B, Member 1
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Antineoplastic Agents
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Dibenzocycloheptenes
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Quinolines
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Vincristine
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Etoposide
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Doxorubicin
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zosuquidar trihydrochloride
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Paclitaxel