Ontology type: schema:ScholarlyArticle Open Access: True
2008-02-13
AUTHORSRuoping Tang, Anne-Marie Faussat, Jean-Yves Perrot, Zora Marjanovic, Simy Cohen, Thomas Storme, Hamid Morjani, Ollivier Legrand, Jean-Pierre Marie
ABSTRACTBackgroundChemotherapeutic drug efflux via the P-glycoprotein (P-gp) transporter encoded by the MDR1/ABCB1 gene is a significant cause of drug resistance in numerous malignancies, including acute leukemias, especially in older patients with acute myeloid leukemia (AML). Therefore, the P-gp modulators that block P-gp-mediated drug efflux have been developed, and used in combination with standard chemotherapy. In this paper, the capacity of zosuquidar, a specific P-gp modulator, to reverse chemoresistance was examined in both leukemia cell lines and primary AML blasts.MethodsThe transporter protein expressions were analyzed by flow cytometry using their specific antibodies. The protein functionalities were assessed by the uptake of their fluorescence substrates in presence or absence their specific modulators. The drug cytotoxicity was evaluated by MTT test.ResultsZosuquidar completely or partially restored drug sensitivity in all P-gp-expressing leukemia cell lines tested and enhanced the cytotoxicity of anthracyclines (daunorubicin, idarubicin, mitoxantrone) and gemtuzumab ozogamicin (Mylotarg) in primary AML blasts with active P-gp. In addition, P-gp inhibition by zosuquidar was found to be more potent than cyclosporine A in cells with highly active P-gp.ConclusionThese in vitro studies suggest that zosuquidar may be an effective adjunct to cytotoxic chemotherapy for AML patients whose blasts express P-gp, especially for older patients. More... »
PAGES51
http://scigraph.springernature.com/pub.10.1186/1471-2407-8-51
DOIhttp://dx.doi.org/10.1186/1471-2407-8-51
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PUBMEDhttps://www.ncbi.nlm.nih.gov/pubmed/18271955
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