ALPHA-FETOPROTEIN AS A TNF RESISTANCE FACTOR FOR THE HUMAN HEPATOCARCINOMA CELL-LINE HEPG2

Human hepatocarcinoma HepG2 cells are known to be insensitive to tumor necrosis factor (TNF) cytotoxicity. In this report, preliminary washi ng of HepG2 cells with serum-free medium to remove endogenous and exog enous alpha-fetoprotein (AFP) from the cultivation medium transfers ce lls from the TNF-resistant to the TNF-sensitive state without addition of any transcriptional inhibitors, HepG2 cells sensitized to by washi ng again became TNF-resistant after their treatment with exogenous AFP . Protective AFP activity against TNF-induced cytotoxicity directly de pends on the AFP/TNF concentration ratio, demonstrating biphasic AFP a ctivity, Our data show that 0.2 mg/ml of AFP acts synergistically to e nhance cytotoxicity of suboptimal TNF doses, In contrast, the same AFP dose significantly attenuates the cytotoxicity of high TNF doses. It is concluded that AFP can function as a protective factor against TNF cytotoxicity in human hepatoma cells, These observations suggest that AFP secretion by certain tumor cells allows a highly flexible regulati on of TNF cytotoxicity. dependent on the amount of endogenous AFP.