Abstract
Eight cell lines were established from the pleural effusion of 4 patients with malignant mesothelioma. The most sensitive (FCCMES-4) and the most resistant (FCCMES-2) mesothelioma cell lines had IC50 of 0.66 and 1.85 microM for doxorubicin in clonogenic assays, respectively. In comparison with murine leukemic P388 cells, mesothelioma cell lines were 7.5- to 21-fold more resistant to doxorubicin. Co-incubation with verapamil significantly increased doxorubicin retention in one of the cell lines (FCCMES-2) expressing P-glycoprotein in 16.8% of the cells. These results indicate that doxorubicin resistance may be intrinsic in refractory mesothelioma patients and P-glycoprotein-mediated drug efflux may be involved in resistance of some of the mesotheliomas.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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ATP Binding Cassette Transporter, Subfamily B, Member 1
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Carrier Proteins / physiology
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Cell Division / drug effects
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DNA, Neoplasm / analysis
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DNA, Neoplasm / genetics
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Doxorubicin / pharmacokinetics*
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Doxorubicin / pharmacology
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Drug Resistance
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Drug Screening Assays, Antitumor
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Flow Cytometry
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Humans
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Membrane Glycoproteins / physiology
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Mesothelioma / drug therapy
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Mesothelioma / metabolism*
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Pleural Effusion, Malignant / pathology
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Ploidies
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Tumor Cells, Cultured / drug effects
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Verapamil / pharmacology
Substances
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ATP Binding Cassette Transporter, Subfamily B, Member 1
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Carrier Proteins
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DNA, Neoplasm
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Membrane Glycoproteins
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Doxorubicin
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Verapamil