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Related Experiment Videos

Multidrug resistance.

J H Gerlach, N Kartner, D R Bell

    Cancer Surveys
    |January 1, 1986
    PubMed
    Summary
    This summary is machine-generated.

    Multidrug resistance, characterized by resistance to multiple anticancer drugs, is often linked to reduced drug accumulation. P-glycoprotein, a plasma membrane protein, is consistently overexpressed in resistant cells and may drive this phenomenon.

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    Area of Science:

    • Biochemistry
    • Molecular Biology
    • Oncology

    Background:

    • Multidrug resistance (MDR) is a complex phenotype where cells resist diverse cytotoxic compounds, including anticancer agents.
    • This resistance is frequently observed in cell lines and tumors selected for single-drug resistance.
    • Reduced cellular drug accumulation, due to altered influx or efflux, underlies this resistance.

    Purpose of the Study:

    • To investigate the molecular mechanisms contributing to multidrug resistance.
    • To identify key cellular changes associated with the multidrug resistance phenotype.
    • To explore the role of P-glycoprotein in mediating drug resistance.

    Main Methods:

    • Selection of mammalian cell lines and transplantable tumors for drug resistance.

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  • Analysis of cellular drug accumulation and transport.
  • Biochemical characterization of resistant cell lines, focusing on protein expression.
  • Investigation of gene amplification in multidrug resistant cells.

    • Main Results:

    • Reduced cellular accumulation of drugs is a primary feature of multidrug resistance.
    • Increased expression of P-glycoprotein, a plasma membrane glycoprotein, is consistently observed in resistant cells.
    • P-glycoprotein expression levels correlate with the degree of drug resistance.
    • Gene amplification of P-glycoprotein observed in some resistant cell lines.
    • P-glycoprotein detected in human ovarian and sarcoma tumors, suggesting its role in clinical malignancies.

    Conclusions:

    • P-glycoprotein is strongly implicated as the causative molecule mediating the multidrug resistance phenotype.
    • The presence of multidrug resistant tumor cells expressing P-glycoprotein in human cancers may impact chemotherapy outcomes.
    • Further research into P-glycoprotein function and its role in cancer is warranted.