Sensitivity of multidrug-resistant MCF-7 cells to a transferrin-doxorubicin conjugate.
Two multidrug-resistant breast cancer cell lines (MCF-7/AdrVp and MCF-7/D.40) each expressing a different membrane protein, involved in the drug resistance, have been treated with a transferrin-doxorubicin conjugate. Conjugates have shown an increase of activity over free doxorubicin on these resistant cell lines. Growth inhibition of doxorubicin-resistant cells, as evaluated by the MTT-assay, was higher for conjugates than for free doxorubicin especially for a 4-day contact period. I D 50 were twice and 10-fold lower for the conjugate than for free doxorubicin on resistant cells. MCF-7/AdrVp seemed to be particularly affected by the conjugate even if its intracellular content of doxorubicin was similar. With the Trf-Dox conjugate, an inverted correlation does exist between the drug-DNA content and the cytotoxicity of the conjugate. Verapamil influenced the uptake of free doxorubicin but not the uptake of Trf-Dox conjugate, thus showing a different mechanism of entry.
Department of Biochemistry, Faculty of Medicine, Université Laval, Québec, Canada.
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D001692:Biological Transport; D001943:Breast Neoplasms; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D002999:Clone Cells; D004317:Doxorubicin / Q000378:metabolism / Q000633:toxicity*; D004351:Drug Resistance; D005260:Female; D006801:Humans; D013997:Time Factors; D014168:Transferrin / Q000378:metabolism / Q000633:toxicity*; D014407:Tumor Cells, Cultured
D014168:Transferrin; D004317:Doxorubicin