Synergistic Antitumor Effects of Tumor Necrosis Factor and γ-Interferon on Human Colon Carcinoma Cell Lines

J. H. Schiller, G. Bittner, B. Storer, J. K V Willson

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67 Scopus citations

Abstract

We assessed the antiproliferative effects of tumor necrosis factor (TNF-a) and 7-interferon (IFN-7) alone and in combination, on nine human colon carcinoma cell lines. All were resistant (<30% inhibition) to TNF-a alone. Four cell lines were resistant to IFN-7 alone, two exhibited a minimal degree of sensitivity (30-50% inhibition), one was moderately sensitive, and two were inhibited 70% or greater. A synergistic antiproliferative effect occurred in eight of the nine cell lines treated with a combination of TNF-a and IFN-7. In seven of these eight, the combination of cytokines resulted in 30-40% more growth inhibition than predicted had an additive interaction occurred (P < 0.005). In two cell lines with an induced resistance to mitomycin C, an increase in resistance to combined TNF-a and IFN-7 treatment correlated with an increasing resistance to mitomycin C. The data were further analyzed to determine if combination treatment altered the sensitivity of the cells to one or both agents in addition to synergistically potentiating growth inhibitory effects. Combinations of TNF-a/IFN-7 enhanced the dose response activity of TNF-a in three cell lines (P ≤0.09) and decreased the dose response activity of IFN-7 in another three (P ≤ 0.02). Colony forming experiments on HCT 116 cells demonstrated a reduction in the number of 250-μm colonies in the IFN-7/TNF-a treatment groups when compared to controls, indicating that combined treatment had a cytotoxic effect. We conclude that combination TNF-a/IFN-7 treatment has a synergistic cytotoxic effect on human colon carcinoma cells. IFN-7 may enhance the effectiveness of TNF-a in some cell lines, but not conversely. These results may have therapeutic implications.

Original languageEnglish (US)
Pages (from-to)2809-2813
Number of pages5
JournalCancer research
Volume47
Issue number11
StatePublished - Jun 1 1987

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Schiller, J. H., Bittner, G., Storer, B., & Willson, J. K. V. (1987). Synergistic Antitumor Effects of Tumor Necrosis Factor and γ-Interferon on Human Colon Carcinoma Cell Lines. Cancer research, 47(11), 2809-2813.