Hyperthermic enhancement of the antitumor effect of natural human tumor necrosis factor-alpha and -beta: an in vitro and in vivo study.
A synergistic antitumor effect of natural human tumor necrosis factor-beta (TNF-beta) in combination with hyperthermia was found, in comparison with that of TNF-alpha, using an in vitro antiproliferative assay on a human colon cancer cell line (RPMI4788) and an in vivo tumor growth inhibition assay on Meth A sarcoma cells. In vitro combined treatment with TNF-beta (10,000 U/ml) and hyperthermia (at 43 degrees for 60 min) synergistically inhibited the proliferation of the cells. Combined effects of TNF-alpha or natural human interferon-alpha or -gamma (IFN-alpha, -gamma) and hyperthermia were also examined, and furthermore, the combinations of TNFs and IFNs were examined in combination with hyperthermia at 42 degrees; their antiproliferative effects were further augmented by hyperthermia. In vivo growth of Meth A sarcoma cells (5 x 10(5)), transplanted subcutaneously into BALB/c mice, was inhibited significantly (P less than 0.05) with the combination of TNF-alpha or -beta (2 x 10(5) U/mouse) and hyperthermia (at 43 degrees for 60 min) as compared to either a single intravenous injection of TNF-alpha or -beta alone or the hyperthermia alone. The influence of TNF-beta and hyperthermia on the cell cycle was examined. Flow cytometric analysis showed that RPMI4788 cells treated with TNF-alpha or -beta accumulated in the S phase of the cell cycle, and that hyperthermia (at 42 degrees for 60 min) alone had no influence on the cell cycle and did not augment the S phase accumulation of the cells treated with TNF-alpha or -beta.
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D003110:Colonic Neoplasms / Q000473:pathology / Q000628:therapy*; D005434:Flow Cytometry; D006801:Humans; D006979:Hyperthermia, Induced; D007370:Interferon Type I / Q000627:therapeutic use; D007371:Interferon-gamma / Q000627:therapeutic use; D012513:Sarcoma, Experimental / Q000473:pathology / Q000628:therapy; D014409:Tumor Necrosis Factor-alpha / Q000627:therapeutic use*
D007370:Interferon Type I; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma