重组腺病毒Ad-hTERTp-HSV-TK/GCV系统的构建及其对人肝癌细胞HepG2的杀伤作用及旁观者效应研究  

Lethal and bystander effects of recombinant adenoviruses with hTERTP-HSV-TK/GCV system on human hepatocellular carcinoma cells HepG2

作　　者：刘燕[1] 邓志华[1] 杨长青[1] 刘京龙[1] 贾静[1] 郭素雅[1] 杨强[1] 

机构地区：[1]山西医科大学第二医院消化科,山西太原030001

出　　处：《中国癌症杂志》2009年第1期29-32,共4页China Oncology

基　　金：国家自然科学基金(No.30672405)

摘　　要：背景与目的:肝癌的基因治疗已成为肝癌治疗的重要发展方向,本文探讨Ad-hTERTP-HSV-TK/GCV系统对人肝癌细胞株HepG2的杀伤作用;并观察其过程中旁观者效应的作用。方法:用重组腺病毒Ad-hTERTP-HSV-TK系统分别感染肝癌细胞株HepG2和正常肝细胞L-02,加入前体药物更昔洛韦(GCV),四甲基偶氮唑盐比色法检测其对感染后细胞的杀伤作用;将感染后的TK阳性HepG2细胞和未感染的TK阴性HepG2细胞按不同比例浓度(0∶10、1∶9、2∶8、3∶7、4∶6、5∶5、6∶4、7∶3、8∶2、9∶1、10∶0)混合,观察其旁观者效应。结果:肝癌细胞HepG2的存活率随病毒感染复数(MOI)和GCV浓度增加而逐渐降低,L-02细胞无明显变化。旁观者效应表明,在TK阳性HepG2细胞为10%时,细胞抑制率达28.06%,70%时达90.44%。结论:重组腺病Ad-hTERTP-HSV-tk/GCV系统对肝癌细胞HepG2有选择性杀伤作用及明显的旁观者效应。Background and purpose： Gene therapy has become more and more popular in the treatment of hepatocellular carcinoma. We observed the lethal effect of Ad-hTERTp-HSV-TK/GCV system and its bystander effect on the hepatocellular carcinoma cells HepG2. Methods： Firstly, proliferation of the HepG2 cells and the L-02 cells was assayed by methyl thiazolyl tetrazolium（MTT） after they were transducted by the recombinant adenovirus and GCV were added of different concentrations. Secondly, we observed the inhibition ratio on HepG2 cells after mixing the transducted HepG2 cells and the non-transducted HepG2 cells. Results： The survival rate of the HepG2 cells was decreased following the increase of the MOI and the concentration of GCV. The bystander effect was significant, the 90.44% of HepG2 cells were inhibited when 70% of HepG2 cells were transducted. Conclusion： The Ad-hTERTp- HSV-TK/GCV system can selectively inhibit the HepG2 cells and has a significant bystander effect on them.

关 键 词：基因治疗 肝肿瘤 重组腺病毒载体 HTERT启动子 自杀基因 培养的肿瘤细胞 

分 类 号：R73-362[医药卫生—肿瘤]