Background: Tumor microenviroment is characteristic of inflammation, ischemia and starvation of nutrient. TNF-a,\r\nwhich is an extraordinarily pleiotropic cytokine, could be an endogenous tumor promoter in some tumor types.\r\nThe basic objective of this study was to investigate the effects of TNF-a on the cell viability and apoptosis of\r\nhepatocellular carcinoma cells under serum starvation, and to identify the molecular mechanisms involved.\r\nMethods: For this purpose, five different concentrations of TNF-a and two different serum settings (serum-cultured\r\nand serum-deprived) were used to investigate the effects of TNF-a on the cell viability and apoptosis of Hep3B and\r\nSMMC-7721 cells.\r\nResults: TNF-a (10 ng/ml) attenuated serum starvation-induced apoptosis of hepatocellular carcinoma cells, and\r\nautophagy conferred this process. BAY11-7082, a specific inhibitor of NF-?B, reversed the suppression of serum\r\nstarvation-induced apoptosis by TNF-a. Moreover, TNF-a-induced NF-?B transactivation was suppressed by autophagy\r\ninhibitor 3-MA. In addition, TNF-a up-regulated Ferritin heavy chain (FHC) transiently by NF-?B activation and FHC levels\r\nwere correlated with the TNF-a-induced protection against serum starvation-mediated apoptosis of hepatocellular\r\ncarcinoma cells. Furthermore, FHC-mediated inhibition of apoptosis depended on suppressing ROS accumulation.\r\nConclusions: Our findings suggested that autophagy conferred the TNF-a protection against serum\r\nstarvation-mediated apoptosis of hepatocellular carcinoma cells, the mechanism involved with the activation of\r\nthe TNF-a/ NF-?B /FHC signaling pathway.
Loading....