Synergistic effects of interferon-γ and tumor necrosis factor against proliferation of gynecologic tumor cell lines

Abstract

The cooperative effects of recombinant human tumor necrosis factor (rH-TNF) and recombinant human interferon-γ (rH-IFN-γ) against the proliferation of four human gynecologic tumor cell lines (HHUA, ISHIKAWA, HeLa S3, and SCH) were examined in vitro. The effect of rH-IFN-γ on TNF receptors was also examined. ISHIKAWA and SCH cells were highly responsive to rH-TNF alone, HHUA cells exhibited a minimal degree of responsiveness to rH-TNF, and HeLa S3 cells were unresponsive to rH-TNF alone. HHUA, HeLa S3, and SCH cells were responsive dose-dependently to rH-IFN-γ, and ISHIKAWA cells were unresponsive to rH-IFN-γ alone. A synergistic antiproliferative effect of rH-TNF and rH-IFN-γ appeared in HHUA, ISHIKAWA, and HeLa S3 cells. The effectiveness of rH-TNF increased in these cell lines pretreated with rH-IFN-γ, but not vice versa. rH-IFN-γ did not change the binding affinity of TNF receptors in the four cell lines, but increased the number of binding sites for TNF in HeLa S3 and SCH cells. These findings suggest that there is no relationship between the increase in TNF binding sites by rH-IFN-γ and the synergistic antiproliferative effect of rH-IFN-γ and rH-TNF. The combination therapy of rH-IFN-γ and rH-TNF will be a new approach against cancers.