Synergistic effects of interferon-gamma and tumor necrosis factor against proliferation of gynecologic tumor cell lines.
The cooperative effects of recombinant human tumor necrosis factor (rH-TNF) and recombinant human interferon-gamma (rH-IFN-gamma) 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-gamma 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-gamma, and ISHIKAWA cells were unresponsive to rH-IFN-gamma alone. A synergistic antiproliferative effect of rH-TNF and rH-IFN-gamma appeared in HHUA, ISHIKAWA, and HeLa S3 cells. The effectiveness of rH-TNF increased in these cell lines pretreated with rH-IFN-gamma, but not vice versa. rH-IFN-gamma 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-gamma and the synergistic antiproliferative effect of rH-IFN-gamma and rH-TNF. The combination therapy of rH-IFN-gamma and rH-TNF will be a new approach against cancers.
Mori
H
H
Department of Obstetrics and Gynecology, Gifu University School of Medicine, Japan.
Kondoh
H
H
Tamaya
T
T
D002455:Cell Division / Q000187:drug effects; D004357:Drug Synergism; D005260:Female; D005833:Genital Neoplasms, Female / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D011994:Recombinant Proteins; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology*
D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma