Ad-hTERT-HSV-tk-GCV系统治疗人膀胱癌裸鼠移植瘤实验探究.docVIP

Ad-hTERT-HSV-tk/GCV系统治疗人膀胱癌裸鼠移植瘤实验探究 　 作者：连文峰，林向阳，张素英，王春仙，杨永安，于洋，宫香宇，陈艳军，张敏 【摘要】 目的 探讨带有人端粒酶逆转录酶（Human Telomerase Reverse Transcriptase，hTERT）启动子驱动单纯疱疹病毒胸腺嘧啶激酶（herpes simplex virus-thymidine kinase，HSV-tk）基因的重组腺病毒（Ad-tk）结合无毒的环氧鸟苷（gancyclovir，GCV）对人膀胱癌的治疗作用。 方法 建立人膀胱癌（人膀胱癌细胞株253J）BALB/C裸小鼠移植瘤模型 , 采用hTERT为启动子驱动Ad-HSV-TK肿瘤局部注射荷瘤小鼠后 ,腹腔注射GCV治疗并观察结果。 结果 单纯Ad-hTERT-HSV-tk和单纯GCV对肿瘤生长无抑制或促进作用；而经过Ad-hTERT-HSV-tk/GCV治疗的裸鼠，显示出明显的肿瘤抑制作用，其体积显著低于各对照组（Plt;0.01），其中一裸鼠肿瘤几乎消失，其肿瘤抑制率达72.5％。 结论 异种动物移植253J细胞后，Ad-hTERT-HSV-tk/GCV系统对体内膀胱肿瘤的生长有明显抑制作用。hTERT启动子调控腺病毒介导的HSV-tk/GCV基因系统能成功靶向性转入人膀胱癌细胞，治疗人膀胱癌效果显著，这为临床上应用自杀基因治疗晚期恶性肿瘤提供了新的思路。 【关键词】 膀胱癌；基因治疗；重组腺病毒；人端粒酶逆转录酶 The animal research of adenoviral mediated HSV-tk/GCV suicide gene system controlled by HTERT promoter on human bladder cancer 【Abstract】 Objective To approach the treatment efficiency of replication defective adenovirus carrying HSV/TK gene under control of the human telomerase reverse transcriptase（hTERT） promoter and ganciclovir （GCV） in a mouse xenografts model of bladder cancer. Methods We erect the model of human bladder cancer （bladder cancer cell line 253J）xenografts in BALB/C nude mouse followed by peritoneal injection of GCV. Results GCV and Ad-hTERTp-HSV-tk alone caused no effect on tumor growth. Therefore Ad-hTERTp-HSV-tk /GCV system was more effectively suppressed on tumor growth of nude mouse .The tumor volume was obviously small as compared to any control group. The tumor was disappeared in one of them. The inhibition of tumor growth reached 72.5%. Conclusion Ad-hTERT-TK/GCV system is highly efficacious to suppress the growth of human bladder cancer in vivo which was injected with bladder cancer cell line 253J. HSV-tk/GCV suicide gene system controlled by HTERT promoter can be selective shifted to human bladder cancer cell. And the effect is obvious, so it may be provide a new idea for treating ending malignancy in clinical use. 【Key words】 bladder cancer;gene therapy;recombinant adenovirus;hTERT HSV-tk/GCV系统是肿瘤