Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Cisplatin and CCNU synergism in spheroid cell subpopulations

Abstract

The cytotoxicity of two antineoplastic drugs, cisplatin and CCNU, was evaluated in Chinese hamster V79 multicell spheroids using the drugs as single agents or combinations. Cells obtained from different depths within spheroids 550-750 microns in diameter showed different sensitivities to the two agents; the external cells of the spheroids were more sensitive than the internal cells to cisplatin, whereas the internal cells were most effectively killed by CCNU. Combining the two agents produced the expected 'complementary' activity, and in addition, synergism was observed between the drugs at exposure levels practical for clinical use. For the combination treatments, both the net pattern of cell killing through the spheroid and the degree of interaction between the agents (quantified using the combination index method) were a function of the dose ratio of the two drugs, and of overall treatment intensity. BCNU produced patterns of cell killing similar to CCNU, but showed little interaction with cisplatin. Our results suggest significant clinical potential in using CCNU with cisplatin, particularly since CCNU-cisplatin combinations were synergistic even in the cell subpopulations most resistant to each drug as a single agent.

Author information

Affiliations

Authors

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Durand, R. Cisplatin and CCNU synergism in spheroid cell subpopulations. Br J Cancer 62, 947–953 (1990). https://doi.org/10.1038/bjc.1990.415

Download citation

Further reading

Search

Quick links