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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)对人前列腺癌的治疗作用。方法建立人前列腺癌裸鼠移植瘤模型,肿瘤局部注射1.0×10~9pfu/ml 重组腺病毒0.1 ml 后,腹腔注射 GCV 100 mg/kg,观察肿瘤体积、瘤重、肿瘤抑制率、肿瘤体积-时间曲线以及裸鼠生存期。取肿瘤组织应用 TUNEL 法及透射电镜检查检测肿瘤细胞凋亡,免疫组化染色检测增殖细胞核抗原,测定增殖指数。结果 Ad-hTERT-HSV-tk 对裸鼠移植瘤具有明显抑制作用,Ad-hTERT-HSV-tk/GCV治疗组的移植瘤体积、重量都明显小于对照组(P<0.05),也明显小于 Ad-hTERT-HSV-tk 和 GCV 治疗组(P<0.05);TUNEL 法测定该系统所致的凋亡率明显高于对照组,而增殖指数明显低于对照组。结论 Ad-hTERT-HSV-tk 联合 GCV 对前列腺癌具有明确的抑制肿瘤生长作用,为前列腺痛的基因治疗提供了一个新的思路。
Objective To investigate the effect of recombinant adenovirus Ad-hTERT-HSV-tk combined with non-toxic guanosine monophosphate (GCV) with human telomerase reverse transcriptase (hTERT) promoter on HSV- Therapeutic effect on human prostate cancer. Methods The human prostate cancer xenografted model was established. The tumor was injected intraperitoneally with 0.1 ml recombinant adenovirus (1.0 × 10 ~ 9pfu / ml). The tumor volume, tumor weight, tumor inhibition rate, Time curve and survival of nude mice. The TUNEL method and transmission electron microscopy were used to detect the tumor cell apoptosis. The proliferating cell nuclear antigen was detected by immunohistochemical staining and the proliferation index was determined. Results Ad-hTERT-HSV-tk significantly inhibited the transplanted xenografts in nude mice. The volume and weight of transplanted tumor in Ad-hTERT-HSV-tk / GCV group were significantly smaller than those in control group (P <0.05) -hTERT-HSV-tk and GCV treatment groups (P <0.05). The apoptotic rate induced by this system was significantly higher than that of the control group by TUNEL assay, while the proliferation index was significantly lower than that of the control group. Conclusions Ad-hTERT-HSV-tk combined with GCV has a clear inhibitory effect on the growth of prostate cancer and provides a new idea for the gene therapy of prostatic pain.