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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 effect of recombinant adenovirus Ad-hTERT-HSV-tk combined with the non-toxic guanosine monophosphate (GCV) gene driven by the human telomerase reverse transcriptase (hTERT) promoter on the HSV-tk gene ) On the treatment of human bladder cancer. Methods: The human bladder cancer cell line 253JBALB / C xenograft model was established. The tail vein of Ad-hTERT-HSV-tk nude mice was injected with intraperitoneal injection of GCV and the results were observed. Tumor destruction and safety were observed by routine pathological sections. Apoptosis was further observed by TUNEL staining and proliferating cell nuclear antigen (PCNA) by immunohistochemistry. Results: Ad-hTERT-HSV-tk / GCV treatment group showed obvious tumor inhibition, the tumor volume and weight were significantly lower than those of the control group (P <0.05), and the tumor inhibition rate was obvious. The apoptotic index of Ad-hTERT-HSV-tk / GCV treatment group was higher than that of other groups, while the proliferation index was significantly lower than that of other groups. Conclusion: Ad-hTERT-HSV-tk / GCV system can significantly inhibit the growth of transplanted xenografts in nude mice and can be targetedly transplanted into human bladder cancer cells with significant therapeutic effect.