人端粒酶逆转录酶启动子调控腺病毒介导胸苷激酶基因治疗人膀胱癌的动物实验研究

Animal Research using the Adenovirus-mediated HSV-TK/GCV Suicide Gene System Controlled by the hTERT Promoter in Human Bladder Cancer

目的:探讨带有人端粒酶逆转录酶(hTERT)启动子驱动单纯疱疹病毒胸腺嘧啶激酶(HSV-tk)基因的重组腺病毒Ad-hTERT-HSV-tk结合无毒的环氧鸟苷(GCV)对人膀胱癌的治疗作用。方法:建立人膀胱癌细胞株253JBALB/C裸小鼠移植瘤模型,采用Ad-hTERT-HSV-tk裸鼠尾静脉注射,腹腔注射GCV治疗并观察结果。通过常规病理切片观察肿瘤破坏情况及安全性;通过TUNEL染色进一步观察肿瘤的凋亡情况,免疫组化法测定增值细胞核抗原(PCNA)。结果:Ad-hTERT-HSV-tk/GCV治疗组,显示出明显的肿瘤抑制作用,其肿瘤体积、重量显著低于各对照组(P<0.05),抑瘤率明显。Ad-hTERT-HSV-tk/GCV治疗组凋亡指数高于其它各组,而增殖指数却明显低于其它各组。结论:Ad-hTERT-HSV-tk/GCV系统对裸鼠移植瘤的生长有明显抑制作用,可以靶向性转入人膀胱癌细胞,治疗效果显著。

Objective： To investigate the HSV/TK gene under the control of the human efficacy of replication-deficient adenovirus carrying the telomerase reverse transcriptase （hTERT） promoter and ganciclovir （GCV） in a mouse xenograft model of bladder cancer. Methods： We established the model of human bladder cancer cell line 253J xenografts in BALB/C nude mice and administered peritoneal injections of GCV and tail vein injections of Ad-hTERT-HSV-tk. Results： The Ad-hTERT-HSV-tk/ GCV system more effectively suppressed tumor growth in nude mice. The tumor volume and weight were obviously smaller compared to the control group. The apoptosis index of the Ad-hTERT-HSV-tk/ GCV group was obviously higher than any other group, but the proliferation index of the Ad-hTERT- HSV-tk/GCV group was lower than in the other groups. Conclusion： The Ad-hTERT-HSV-tk/GCV system suppresses the growth of human bladder cancer in vivo. The HSV-TK/GCV suicide gene system controlled by the hTERT promoter can be used to treat human bladder cancer, and the effect is significant.