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Reduced drug accumulation in multiply drug-resistant human KB carcinoma cell lines

A Fojo, S Akiyama, M M Gottesman

    Cancer Research
    |July 1, 1985
    PubMed

    Insights

    Human KB cells developed resistance to chemotherapy drugs through altered drug uptake and efflux. Verapamil partially reversed this multiple drug resistance by enhancing drug accumulation in resistant cells.

    Area of Science:

    • Cell Biology
    • Pharmacology
    • Cancer Research

    Background:

    • Multidrug resistance (MDR) is a major challenge in cancer chemotherapy.
    • Understanding the mechanisms of MDR is crucial for developing effective treatment strategies.

    Purpose of the Study:

    • To characterize drug uptake, accumulation, and efflux in human KB cells with acquired resistance to chemotherapeutic agents.
    • To investigate the effect of verapamil on reversing the multidrug resistance phenotype.

    Main Methods:

    • Isolation of four sequential colchicine-resistant KB cell lines.
    • Quantification of drug uptake and efflux using radiolabeled compounds.
    • Assessment of drug accumulation and sensitivity to various chemotherapeutic agents.
    • Evaluation of verapamil's effect on drug transport and cellular accumulation.

    Main Results:

    • Drug uptake was nonsaturable, and accumulation generally decreased with increasing drug resistance.
    • Rapid drug efflux was observed, with more resistant lines releasing a higher percentage of drug faster.
    • Verapamil partially reversed multidrug resistance by increasing drug uptake and accumulation in resistant cells.

    Conclusions:

    • The development of multidrug resistance in human epithelial cells is a complex process involving alterations in drug uptake, accumulation, and efflux.
    • Targeting drug transport mechanisms, such as with verapamil, may offer a strategy to overcome chemotherapy resistance.

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