腺病毒介导Ad-HSV-TK/GCV自杀基因对人卵巢癌细胞体内杀伤效应研究  

Study on the killing effect of Ad-hTERT-HSV-tk suicide gene system mediated by adenovirus vector on ovarian cancer in vivo

作　　者：王善凤[1] 刘尧 

机构地区：[1]辽宁医学院附属第一医院,辽宁锦州121000 [2]北京市延庆县医院,北京延庆102100

出　　处：《中国现代医学杂志》2013年第36期21-24,共4页China Journal of Modern Medicine

基　　金：辽宁省教育厅科技项目(No:I2010282)

摘　　要：目的观察以腺病毒为载体,人端粒酶逆转录酶(hTERT)为启动子的单纯疱疹病毒胸苷激酶(HSV-TK)基因重构体Ad-hTERT-HSV-tk联合更昔洛韦(GCV)对人卵巢癌细胞(Skov-3)的体内杀伤作用。方法建立人卵巢癌裸鼠移植瘤模型,Ad-hTERT-HSV-tk经尾静脉注射荷瘤小鼠后,腹腔注射GCV,观察肿瘤体积、质量、肿瘤抑制率、肿瘤体积-时间曲线以及生存期,流式细胞术(FCM)检测SKOV-3的凋亡,Western blot法检测各组肿瘤组织中EGFR蛋白表达。结果自杀基因Ad-hTERT-HSV-tk联合GCV系统对人卵巢癌裸鼠移植瘤生长具有明显抑制作用,对移植瘤的体积和瘤质量的抑制作用明显,并促进SKOV-3细胞凋亡,Ad-hTERT-HSV-tk组EGFR蛋白表达水平较其它三组降低(P<0.05)。结论 Ad-hTERT-HSV-tk联合GCV自杀基因系统在裸鼠体内对Skov-3肿瘤呈显著杀伤作用,其机制可能与下调EGFR蛋白表达相关。[ Objective ] To study the killing effect of the HSV-tk suicide gene system with the vector of aden- ovirus, the promoter of Human Telomerase Reverse Transcriptase （Ad-hTERT-HSV-tk）, combined with ganciclovir on human ovarian varcinoma cells in nude mice with tumors. [ Methods ] Construct the human ovarian carcinoma in mice transplanted tumor models, injecting Ad-hTERT-HSV-tk via the tail＇s vein, GCV via abdominal cavity of bearing mice, observe the tumor volume, weight, tumor inhibition rate, the curve of tumor volume-time and surivival period. Flow cytometry technique （FCM） tests SKOV-3 apoptosis, the expression of EGFR were examined by West- ern blot. [Results] Ad-hTERT-HSV-tk combined with GCV suicide gene system on human ovarian cancer xenografts in nude mice inhibited obviously, the tumor volume and tumor weight was significantly inhibited, and pro- mote apoptosis in SKOV-3 cells, the expression of protein of EGFR was down-regulated in Ad-hTERT-HSV-tk group （P 〈0.05）. [ Conclusions ] Ad-hTERT-HSV-tk combined with GCV suicide gene system show significant killing effect on SKOV-3 in nude mice model, the mechanism maybe that Ad-hTERT-HSV-tk system can down- grade the expression of protein of EGFR.

关 键 词：卵巢癌 基因治疗 腺病毒 

分 类 号：R737.31[医药卫生—肿瘤]