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Chemosensitivity testing in V79 spheroids: drug delivery and cellular microenvironment.

R E Durand

    Journal of the National Cancer Institute
    |July 1, 1986
    PubMed
    Summary

    Chemotherapy resistance in solid tumors was studied using multicellular spheroids. The spheroid

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    Area of Science:

    • Cell biology
    • Cancer research
    • Pharmacology

    Background:

    • Solid tumors often develop cell populations resistant to chemotherapy due to factors like poor blood supply.
    • Multicellular spheroids in tissue culture mimic solid tumors, featuring noncycling and hypoxic cells.

    Purpose of the Study:

    • To investigate the sensitivity of cells within different regions of multicellular spheroids to various chemotherapeutic agents.
    • To differentiate between inherent drug sensitivity and the influence of the spheroid microenvironment on cell resistance.

    Main Methods:

    • Chinese hamster V79 multicell spheroids were cultured.
    • Cell-sorting techniques were employed to isolate cells based on their depth within the spheroids.
    • Sensitivity profiles of cells from different spheroid regions were determined after exposure to doxorubicin, bleomycin, 5-fluorouracil, carmustine, cisplatin, chlorambucil, and mitomycin.
    • Pre-separated cells were exposed to drugs to assess inherent sensitivity versus microenvironment effects.

    Main Results:

    • Drug penetration was only a limiting factor for doxorubicin.
    • The microenvironment within the intact spheroid significantly influenced cell sensitivity to most tested chemotherapeutic agents.
    • Cells located deeper within the spheroid, potentially hypoxic or noncycling, exhibited altered sensitivity profiles.

    Conclusions:

    • The spheroid's microenvironment plays a crucial role in modulating chemotherapy sensitivity, more so than inherent cellular properties or drug penetration for most agents tested.
    • Findings suggest that strategies targeting the tumor microenvironment could enhance chemotherapy efficacy against solid tumors.

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