miR-29c互补序列与AFP启动子在肝癌基因靶向治疗中的应用研究  

Targeted hepatocellular carcinoma gene therapy based on normal cell-specific microRNA29c-targeted sequences (TS) and the AFP promoter

作　　者：张友琴 陶冶 

机构地区：[1]湖南省衡阳市衡南县人民医院,421001

出　　处：《中国现代医药杂志》2013年第8期30-33,共4页Modern Medicine Journal of China

摘　　要：目的建立基于肿瘤特异性启动子和microRNA(miR)互补序列的肝癌基因靶向治疗系统。方法分别检测甲胎蛋白AFP启动子和miR-29c在不同的人肝癌细胞株和正常肝细胞株中的表达活性;比较分析AFP启动子和新的靶向系统AFP-MiR-29c-TS(miR-29c-TS,miR-29c互补序列)在肝癌细胞株中的靶向特征;对比分析AFP-E1A和AFP-MiR-29c-TS-E1A在肝癌治疗中的疗效和特异性差异。结果 AFP启动子在人肝癌细胞株HepG2和Huh7中特异性高表达,miR-29c在人肝细胞株LO2中特异性高表达;在肝细胞株中,AFP-MiR-29c-TS的活性较AFP启动子明显降低(P<0.01);AFP-E1A和AFP-MiR-29c-TS-E1A在肝癌治疗中的疗效差异不具有统计学意义。结论 AFP-MiR-29c-TS是肝癌基因靶向治疗安全、有效的载体系统。Objective To develop a novel vector system based on AFP promoter and cell-specific micmRNA for hepa- toeellular targeted therapy. Methods Evaluated the expression activity of AFP promoter and miR-29e in liver cancer cell lines and normal cell line. And then constructed AFP-MiR-29e-TS and AFP-MiR-29e-TS-E1A system, compared the speci- ficity and killing effects with novel targeted system. Results The expression activity of AFP promoter was higher in HepG2 and Huh7 cells and revealed that MiR-29e was highly expressed in normal liver cells. After incorporating normal cell-specific mieroRNA-targeted sequences, the AFP-MiR-29e-TS systerm decreased its activity compared to AFP promoter in normal cells （P〈0.01）. Moreover, the killing effects of AFP-E1A and AFP-MiR-29e-TS-E1A on liver cancer cell lines had no significant differences. Conclusion AFP-MiR-29c-TS systerm is safe, effective and versatile in hepatocellular carcinoma gene therapy.

关 键 词：肝癌 AFP启动子 microRNA(miR) 靶向治疗 

分 类 号：R735.7[医药卫生—肿瘤]