The synergistic anti-proliferative effect of gamma-interferon and human lymphotoxin.
Highly purified preparations of rHuIFN-gamma and HLT synergistically inhibit the in vitro proliferation of WI38VA13 cells, a SV40 virus-transformed derivative of the human cell line W138. The growth of nontumorigenic WI38 cells, established from normal diploid embryonic lung tissue, was not inhibited under identical incubation conditions; rMuIFN-gamma and HLT have the same in vitro effects on the murine melanoma B16. Thus, the combination of rMuIFN-gamma and HLT synergistically inhibits the growth of B16 cells, although incubation with either lymphokine alone has no significant anti-proliferative effect. Flow cytometric analysis of the cell cycle of asynchronous cells indicates that when B16 melanoma cells are treated with rMuIFN-gamma and HLT in combination, more cells accumulate in the G0/G1 phase than when the cells are treated with rMuIFN-gamma alone. It appears that populations of rapidly proliferating tumor cells, which normally contain a large percentage in the S+G2+M phases of the cell cycle, become arrested in the quiescent G0/G1 phase by the combination of IFN-gamma and HLT, resulting in the inhibition of cell growth.
D000818:Animals; D002453:Cell Cycle; D002455:Cell Division; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000473:pathology; D004357:Drug Synergism; D006131:Growth Inhibitors / Q000502:physiology*; D006801:Humans; D007371:Interferon-gamma / Q000502:physiology*; D008233:Lymphotoxin-alpha / Q000502:physiology*; D008545:Melanoma / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL
D006131:Growth Inhibitors; D008233:Lymphotoxin-alpha; D007371:Interferon-gamma