Synergistic antitumor activity of etoposide and human interleukin-1 alpha against human melanoma cells.
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 A375-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-bromid e) 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-1 alpha 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 IL-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.
Usui
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Division of Cancer Treatment, National Cancer Institute, Bethesda, MD 20892.
Mimnaugh
E G
EG
Sinha
B K
BK
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis; D004249:DNA Damage; D004357:Drug Synergism; D005047:Etoposide / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D007375:Interleukin-1 / Q000008:administration & dosage / Q000494:pharmacology*; D008545:Melanoma / Q000473:pathology*; D011994:Recombinant Proteins / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D007375:Interleukin-1; D011994:Recombinant Proteins; D005047:Etoposide; D004247:DNA