Antitumor Efficacy of Doxorubicin in Combination with Cisplatin on Human Lymphoma Cells at Various Cell Densities in vitro.

概要

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The influence of tumor cell density on the antitumor effect of doxorubicin (DXR) in combination with cisplatin (CDDP) was studied in vitro using DND-39A lymphoma cells. DXR was progressively less effective on colony formation inhibition when cell density was increased from 105 to 108 viable cells/ml (positive inoculum effect), whereas the effect of CDDP was not influenced by cell densities. At a density of 105 cells/ml, inhibition of colony formation was virtually identical irrespective of cells being exposed to DXR and CDDP either simultaneously or sequentially. When cell density was increased to 107 and 108 cells/ml, sequential exposure to CDDP followed by DXR was more active than simultaneous or reversed order of exposure to the two drugs. These results indicate that for DXR-CDDP combination chemotherapy against the cells at high density, the proper sequence of the treatment should be the administration of CDDP followed by DXR, rather than simultaneous or reversed order of exposure. Inoculum effect may be an additional determinant for the rational development of combination chemotherapy.
The Keio Journal of Medicineの論文