The establishment of immuno-chemotherapy through the IFN-IFNAR (IFN-α receptor) signaling pathway for the intractable and advanced hepatocellular carcinoma

1)IFN/5-FU联合治疗肝癌细胞的抗肿瘤作用与IFN-α R的表达强度密切相关。在IFNAR基因转染模型的实验中也证明了这一点。2）TRAIL/TRAIL受体、Fas/FasLIFN-α和5-FU通过增强外周血单个核细胞中TRAIL的表达和肝癌细胞中TRAIL受体的表达而发挥抗肿瘤作用。在外周血细胞中，发现NK细胞对人肝癌细胞具有细胞毒作用。此外，本研究还证实了Fas/FasL系统参与了抗肿瘤作用。Caspase和FLIP介导Fas/FasL系统对肝癌细胞的间接抗肿瘤作用。3）基因表达谱分析以IFN-α和5-FU联合治疗的临床标本为例，基因表达谱分析可用于85%以上的疗效预测。

1)The mechanism of the antitumor effect through the IFN-IFNAR signalingThe anti-tumor effect of IFN/5-FU combined therapy was significantly correlated with the strength of IFNAR expression, in the HCC cells in-vitro. This was also proved in the experiment of the IFNAR gene transfection model. In this mechanism, the upragulation of the p-STATS and Bcl-xl expression were most significantly correlated with anti-tumor effect, among the several signal transductional factors.2)Anti tumor effect through TRAIL/TRAIL receptor and Fas/FasLIFN-α and 5-FU enhanced TRAIL expression in peripheral mononuclear cells, and TRAIL receptor in cultured hepatoma cells. Among peripheral blood cells, NK cells were found to exert the cytotoxic effects on human hepatoma cells. In addition, the involvement of Fas/FasL system in the anti tumor effect was examined and confirmed in this study. The indirect anti-tumor effect for HCC cells through Fas/FasL system was mediated by the Caspase and FLIP.3)The Gene Expression ProfilingUsing the clinical samples treated by IFN-α and 5-FU, the gene expression profiling would be suggested to be useful for the prediction of the treatment efficacy at the over 85%.