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目的XIAP相关因子1(XIAP-associated factor 1,XAF1)可与XIAP直接结合并拮抗其抗凋亡作用。本文研究了XAF1在人体肝癌组织表达,同时探讨了XAF1可能的作用机制。方法通过免疫组化方法检测了XAF1在人体肝癌组织中表达水平;建立稳定高表达XAF1的肝癌细胞克隆,通过基因芯片技术探讨了XAF1可能的作用机制。结果XAF1在人肝癌组织中表达免疫组化实验结果提示,XAF1在人肝癌组织中的表达阳性率为0.56%±0.03%,在癌旁组织中的表达阳性率为5.1±0.023%,两组均值间差异有统计学意义(P<0.05);基因芯片结果提示,7.03%的基因发生的改变有统计学意义。其中1.72%基因与细胞凋亡和细胞周期相关。在细胞凋亡和细胞周期相关基因中,41.9%与线粒体凋亡相关途径相关,可见XAF1可能通过线粒体内源性途径促进凋亡。结论XAF1在人体肝癌组织中表达水平低于癌旁组织;其抑制凋亡反应可能是通过内源性途径机制实现,XAF1有可能成为肝癌基因治疗的新靶点。
Objective XIAP-associated factor 1 (XAF1) binds directly to XIAP and antagonizes its anti-apoptotic effect. In this paper, we studied the expression of XAF1 in human hepatocellular carcinoma and discussed the possible mechanism of XAF1. Methods The expression level of XAF1 in human hepatocellular carcinoma was detected by immunohistochemistry. The stable and highly expressed XAF1 hepatocellular carcinoma cell clone was established. The possible mechanism of XAF1 was explored by gene chip technique. Results The expression of XAF1 in human hepatocellular carcinoma showed that the positive rate of XAF1 in human hepatocellular carcinoma was 0.56% ± 0.03% and in the adjacent tissues was 5.1 ± 0.023% There was significant difference between the two groups (P <0.05). The result of gene microarray showed that the change of 7.03% gene was statistically significant. Among them, 1.72% were related to apoptosis and cell cycle. Among the apoptosis-related and cell cycle-related genes, 41.9% were related to mitochondrial apoptosis-related pathways, suggesting that XAF1 may promote apoptosis through the mitochondrial endogenous pathway. Conclusion The expression of XAF1 in human hepatocellular carcinoma tissue is lower than that in paracancerous tissues. Its inhibitory effect on apoptosis may be mediated by endogenous pathway. XAF1 may be a new target for gene therapy of hepatocellular carcinoma.