Synergistic effects of TGIF and interferon gamma (IFN-gamma) on tumor cell growth. TGIF and IFN-gamma.
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.
Katano
M
M
Department of Surgery, Saga Medical School, Japan.
Yamamoto
H
H
Nakamura
M
M
Matsuo
T
T
Hisatsugu
T
T
D000818:Animals; D001685:Biological Factors / Q000096:biosynthesis / Q000378:metabolism / Q000494:pharmacology*; D001688:Biological Products / Q000096:biosynthesis / Q000378:metabolism / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines; D004357:Drug Synergism; D006131:Growth Inhibitors / Q000096:biosynthesis / Q000378:metabolism / Q000494:pharmacology*; D006168:Guinea Pigs; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D010844:Picibanil / Q000494:pharmacology*; D011994:Recombinant Proteins; D013045:Species Specificity; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
D001685:Biological Factors; D001688:Biological Products; D016207:Cytokines; D006131:Growth Inhibitors; D011994:Recombinant Proteins; D010844:Picibanil; D007371:Interferon-gamma