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.