通过重组腺病毒抑制核因子-κB的基因治疗导致人肝癌细胞凋亡。
Gene therapy that inhibits NF-kappaB results in apoptosis of human hepatocarcinoma by recombinant adenovirus.
作者信息
Li Tie-Jun, Jia Li-Ping, Gao Xiao-Ling, Huang Ai-Long
机构信息
Center of Blood Purification, The 9th Hospital of Chongqing, Beibei 400700, Chongqing, China.
出版信息
World J Gastroenterol. 2006 Sep 7;12(33):5287-92. doi: 10.3748/wjg.v12.i33.5287.
AIM
To investigate whether the recombinant adenovirus induces the TNF-alpha-mediated apoptosis in vivo.
METHODS
Human hepatocarcinoma cell line (HepG(2)) cells were transfected into BALB/c nude mice, and the tumor growth curve was drawn. We analyzed apoptosis in HepG(2) cells by TUNEL, HE staining and electron microscopy.
RESULTS
AdIkappaBalphaM was expressed stably and efficiently in HepG(2) and could not be degraded by induction of TNF-alpha. Tumor growth in mice could be reduced remarkably if treated by AdIkappaBalphaM plus TNF-alpha. There was apoptosis of > 70% of cells treated with AdIkappaBalphaM plus TNF-alpha and about 50% of cells treated with AdIkappaBalphaM. In contrast, there was few cell apoptosis in HepG(2) cells treated with phosphate buffered saline and AdIkappaBalpha. HepG(2) cells in mice also exhibited a high level of apoptosis after in vivo injection with AdIkappaBalphaM. The tumor growth curve indicated the tumor transfected with AdIkappaBalphaM could be restrained.
CONCLUSION
AdIkappaBalphaM gene therapy greatly enhances apoptosis due to inhibition of an NF-kappaB-mediated antiapoptosis signaling pathway.
目的
研究重组腺病毒在体内是否能诱导肿瘤坏死因子-α（TNF-α）介导的细胞凋亡。
方法
将人肝癌细胞系（HepG(2)）细胞接种到BALB/c裸鼠体内，绘制肿瘤生长曲线。通过TUNEL法、苏木精-伊红（HE）染色及电子显微镜分析HepG(2)细胞的凋亡情况。
结果
AdIkappaBalphaM在HepG(2)细胞中稳定高效表达，且不能被TNF-α诱导降解。用AdIkappaBalphaM加TNF-α处理可显著降低小鼠肿瘤生长。AdIkappaBalphaM加TNF-α处理的细胞凋亡率>70%，AdIkappaBalphaM处理的细胞凋亡率约为50%。相比之下，用磷酸盐缓冲盐水和AdIkappaBalpha处理的HepG(2)细胞几乎没有细胞凋亡。给小鼠体内注射AdIkappaBalphaM后，HepG(2)细胞也表现出高水平的凋亡。肿瘤生长曲线表明，转染AdIkappaBalphaM的肿瘤可受到抑制。
结论
AdIkappaBalphaM基因治疗通过抑制核因子-κB（NF-κB）介导的抗凋亡信号通路，大大增强了细胞凋亡。
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