Ad-hTERTp-HSV-TK/GCV系统对肝癌腹水抑制效应的实验研究  

Inhibition of Ad-hTERTp-HSV-tk/GCV system on formation of malignant ascites of hepatocellular carcinoma

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

机构地区：[1]山西医科大学第二附属医院消化科,山西太原030001

出　　处：《中华肿瘤防治杂志》2010年第15期1144-1146,共3页Chinese Journal of Cancer Prevention and Treatment

基　　金：国家自然基金(30672405)

摘　　要：目的:探讨由人端粒酶逆转录酶启动子驱动单纯疱疹病毒胸腺激酶基因的重组腺病毒,联合更昔洛韦(GCV)对肝细胞癌腹水生成的影响。方法:将H22细胞注入小鼠腹腔建立肝癌腹水瘤模型,并通过观察各组小鼠体质量、腹围、腹水量、生存时间、脏器及细胞凋亡率等指标的差异,揭示Ad-hTERTp-HSV-TK/GCV系统对肝癌腹水的治疗作用。结果:经过Ad-hTERTp-HSV-TK/GCV治疗的小鼠,显示出明显的腹水抑制作用,其腹水量显著低于各对照组(P<0.01),生存时间延长(P<0.01),细胞凋亡率提高(P<0.01),并且无明显毒副反应。而单独使用Ad-hTERTp-HSV-TK和GCV对腹水生成无明显作用。结论:Ad-hTERTp-HSV-TK/GCV系统对肝癌细胞有较强的靶向杀伤作用,治疗肝癌腹水效果显著,对其临床应用具有理论意义。OBJECTIVE：To investgate the treatment efficiency of replication defective adenovirus carrying HSV/TK gene under the control of the human telomerase reverse transcriptase （hTERT） promoter and ganciclovir （GCV） on the formation of carcinomatous ascites of hepatocellular carcinoma in mice.METHODS：H22 cells were injected into the peritoneal cavity of mice and the model of ascites was established.The therapeutic effect was evaluated by comparing the change of weights,abdominal circumference,ascites volumes,survival time,organs and apoptosis rate.RESULTS：The Ad-hTERTp-HSV-tk /GCV system obviously inhibited the production of ascites.The ascites volume was obviously small as compared to any control group （P〈0.01）,prolonging the survival period （P〈0.01）,and elevating the apoptosis rates of tumor cells without influencing on internal organs of tumor-bearing mice.But Ad-hTERTp-HSV-tk and GCV alone caused no effect on ascites growth.CONCLUSIONS：The Ad-hTERTp-HSV-tk /GCV system shows target killing effect on hepatoma cells,and the effect is remarkable.It is promising to be used in clinical gene therapy.

关 键 词：胸苷激酶 腺病毒科 基因疗法 肝肿瘤 腹水 端粒 末端转移酶 

分 类 号：R735.7[医药卫生—肿瘤]