S9788 modulation of P-glycoprotein- and Multidrug-related protein-mediated multidrug resistance by Servier 9788 in doxorubicin-resistant MCF7 cells.
Inherent or acquired resistance to multiple natural drugs, termed multidrug resistance (MDR), represents a major obstacle to chemotherapy. Expression of P-glycoprotein (P-gp) in MCF7mdr and MCF7R resistant cells was detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis. MCF7R, but not the MDR1 gene-transfected MCF7mdr cells, expressed multidrug-related protein (MRP) concomitantly. Efficacy of an MDR modulator, designated as Servier 9788 (S9788), was estimated by doxorubicin (Dox) sensitization, Dox incorporation, and functional rhodamine 123 assay on MCF7 cell lines. Results showed that S9788 modulates the P-gp-associated MDR of MCF7mdr cells as well as the Multidrug-related protein-associated MDR of MCF7R cells.
Laboratoire du Service D'Oncologie Medical de la Pitie-Salpetriere, Paris, France.
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Bichat
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Solis-Recendez
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Poullain
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Poupon
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Khayat
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Bastian
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000502:physiology*; D018528:ATP-Binding Cassette Transporters / Q000502:physiology*; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D004317:Doxorubicin / Q000493:pharmacokinetics / Q000494:pharmacology*; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D006801:Humans; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D010880:Piperidines / Q000494:pharmacology*; D020112:Rhodamine 123; D012235:Rhodamines / Q000378:metabolism; D014227:Triazines / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018528:ATP-Binding Cassette Transporters; D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D010880:Piperidines; D020112:Rhodamine 123; D012235:Rhodamines; D014227:Triazines; C077022:S 9788