Characterization of the synergistic antiproliferative effects of interferon-gamma and tumor necrosis factor on human colon carcinoma cell lines

Journal of Interferon Research
J H SchillerM A Horisberger

Abstract

We employed a tumor-type-specific tissue culture model utilizing three human colon carcinoma cell lines to (i) assess the effects of schedule, sequence, dose, and duration of exposure on the antiproliferative activity of combinations of tumor necrosis factor (TNF) and interferon-gamma (IFN-gamma) and to (ii) determine the effects of this combination on the production of a TNF-inducible protein, IFN-beta 2, and an IFN-inducible protein, p78. A statistical model was developed to ascertain the effects of each of three of the variables (sequence, dose, and duration) on the other two. With minor exceptions, the maximal antiproliferative effect in all three cell lines was observed when IFN-gamma and TNF were administered simultaneously, regardless of the doses of each agent and duration of exposure. Exposing the cells to TNF before IFN-gamma resulted in the least inhibition in cell growth. In all three cell lines, the antiproliferative effects of each treatment group were related directly to the duration of exposure. In two of the three cell lines, an intermittent schedule was as effective as a 24-h exposure. No p78 induction was observed in the HCT 116 cell line with IFN-gamma alone, TNF alone, or the combination; p78 was slightly i...Continue Reading

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Citations

Sep 7, 2000·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·M KovaríkováA Kozubík
Mar 1, 1993·Postgraduate Medical Journal·M Odeh
Mar 1, 1993·Postgraduate Medical Journal·P L Selvais, J Henrion

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