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JNCI Journal of the National Cancer Institute 1989 81(24):1904-1909; doi:10.1093/jnci/81.24.1904
© 1989 by Oxford University Press
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Journal of the National Cancer Institute, Vol. 81, No. 24, 1904-1909, December 20, 1989
© 1989 Oxford University Press

Synergistic Antitumor Activity of Etoposide and Human Interleukin-1{alpha} Against Human Melanoma Cells

Noriko Usui, Edward G. Mimnaugh, Birandra K. Sinha*

Medicine Branch, Division of Cancer Treatment, National Cancer Institute Bethesda, MD

* Correspondence to: Dr. Birandra K. Sinha, Bldg. 10, Rm. 6N-1I9, National Institutes of Health, Bethesda, MD 20892.

To investigate the possibility of increased activity of cytotoxic anticancer drugs combined with cytokines, we treated human melanoma cells with combinations of etoposide (VP-16) and human recombinant interleukin-1{alpha} (rIL-1{alpha}). We evaluated the combined cytotoxic effects of VP-16 and rIL-1{alpha} using A37S-C6 cells, which are sensitive to rIL-1{alpha}, and A375-C5 cells, a clonal variant line resistant to rIL-1{alpha}. We used the MTT (3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium-bromide) assay and the inhibition of (3H]thymidine incorporation into DNA. We analyzed data using the median effects principle of Chou and Talalay (Chou's analysis). The calculated combination index values, at a dose ratio of VP-16 to rIL-la of 12: 1 in simultaneous exposure, indicated synergistic cytotoxicity toward both A375-C6 cells and A375-C5 cells. We observed more pronounced synergism with VP-16 and rIL-1{alpha} toward the A375-C5 JL-1{alpha}-resistant melanoma cells. These results suggest that rIL-1{alpha} combined with cytotoxic antitumor drugs may provide increased benefit in the treatment of malignant melanoma. [J Natl Cancer Inst 81: 1904–1909, 1989]


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