The effect of γ-interferon on receptor and cytotoxic response of tumor necrosis factor mutant

PURPOSE: To explore the effect of γ-interferon on tumor necrosis factor receptor (TNFR) of cultured human gastric cancer cells (SGC7901) and the mechanism of anti-tumor synergism of γ-interferon and tumor necrosis factor mutant (TNF-m). METHODS: The 125I-tumor necrosis factor mutant (125I-TNF-m) was used as radioligand. The radioassay was applied to detect the effect of γ-interferon on the expression of TNFR of SGC7901 cells and on the internalization and degradation of TNF-m. MTT colorimetric method was used in studying the anti-tumor synergism of γ-interferon and TNF-m. RESULTS: By virtue of γ-interferon, the amount of TNFR of SGC7901 cells was increased from 0.56 x 10-11 to 0.94 x 10-11 nmol/cell. No effect was shown on the affinity of the receptors (Kd value: 2.78 x 10-10 mol/L versus 2.64 x 10-10 mol/L, t 1.2, P>0.5). γ-interferon could promote the synthesis of TNFR protein; and also markedly increase the absolute amount of the internalization and degradation of TNF-m, but exerted no effect on their ratios. The maximum cancer cell kill rate of TNF-m on SGC7901 was 96% (t = 5.2, P<0.01) under the influence of γ-interferon. CONCLUSIONS: γ-interferon increased the anti-tumor effect in vitro of TNF-m by up-regulating the TNFR