Synergistic effects of TGIF and interferonγ (IFN-γ) on tumor cell growthTGIF and IFN-γ

Abstract

Interferon-gamma (IFN-gamma) and tumor growth inhibitory factor (TGIF) were induced in vitro in the supernatant from mixed culture of human peripheral blood mononuclear cells (PBMC) and OK-432. TGIF activity was determined by growth inhibition of a human gastric adenocarcinoma cell line, MK-1 cells, and IFN-gamma activity was measured by radioimmunoassay. The production of TGIF and IFN-gamma was time-dependent, reaching its maximum around 48 hrs. Although there was no significant correlation between TGIF production and IFN-gamma production, combination of a subthreshold concentration of recombinant IFN-gamma (rIFN-gamma) and TGIF induced significant growth inhibition of MK-1 cells. This fact indicates that the effects of rIFN-gamma and TGIF are synergistic. The antiproliferative effect of these cytokines are highly species-specific, and their synergistic effects were also species-specific. rIFN-gamma-sensitive and -resistant clones were successfully established from the original MK-1 cell line; those clones are both sensitive to TGIF. Synergistic antiproliferative effects were found when the rIFN-gamma-sensitive clone, but not the resistant clone, was used as a target, suggesting that the synergistic effects require the target cells' sensitivity to IFN-gamma. These results indicate that the synergistic effects of TGIF and IFN-gamma may produce a clinical antitumor action in cancer patients receiving OK-432 administration.