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Using growth delay and clonogenic cell survival as end points, we have shown that the 3-dimensional structure of human lung tumour spheroids confers a degree of resistance to the anthracyclines doxorubicin and 4'-deoxydoxorubicin, relative to cells grown as monolayer. 4'-deoxydoxorubicin induces a longer growth delay and greater clonogenic cell kill than doxorubicin in spheroids, although it is no more cytotoxic in monolayer. Using fluorescent microscopy we have demonstrated, qualitatively, that lipophilic anthracycline analogues partition into the spheroid more rapidly and to a greater degree than doxorubicin. It is apparent that penetration is an important aspect of anthracycline drug resistance in spheroids, and the spheroid model may represent a better in vitro system for testing lipophilic analogues of cytotoxic drugs.

Original publication

DOI

10.1089/cdd.1987.4.63

Type

Journal article

Journal

Cancer Drug Deliv

Publication Date

1987

Volume

4

Pages

63 - 74

Keywords

Antibiotics, Antineoplastic, Cell Survival, Daunorubicin, Doxorubicin, Drug Screening Assays, Antitumor, Humans, Lung Neoplasms, Microscopy, Fluorescence, Tumor Cells, Cultured