hTERT启动子联合HSV-tk/GCV对人前列癌裸鼠移植瘤的治疗作用

hTERT Promotor Associated HSV-tk/GCV System Therapy Effect on Nude Mice Xenografts Model of Human Prostate Cancer

目的观察以人端粒酶逆转录酶(Human Telomerase Reverse Transcriptase promoter,hTERT)为启动子,以腺病毒为载体的单纯疱疹病毒胸苷激酶基因重组构建体Ad-hTERT-HSV-tk联合更昔洛韦(GCV)体内抗前列腺癌的活性。方法建立前列腺癌裸鼠移植瘤模型,按不同浓度梯度Ad-hTERT-HSV-tk经尾静脉注射荷瘤小鼠后,腹腔注射同一浓度GCV,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。评价Ad-hTERT-HSV-tk的抗肿瘤活性。结果在作用底物GCV存在条件下,Ad-hTERT-HSV-tk对人前列腺癌裸鼠移植瘤生长具有明显抑制作用,对移植瘤的体积和瘤重的抑制效应与Ad-hTERT-HSV-tk呈剂量依赖性增强,且未达量效平台期。将Ad-hTERT-HSV-tk和GCV分别单独应用,结果显示对肿瘤生长均有一定的抑制作用,但与阴性对照组相比,差异无统计学意义(P>0.05)。结论Ad-hTERT-HSV-tk联合GCV对前列腺癌具有明确的实验性治疗作用,值得进一步研究,在人类前列腺癌治疗方面具有明显的临床运用前景。

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 gancyclovir（GCV） in nude mice xenografts model of prostate cancer.Methods We successfully build the model of human prostate cancer xenografts in BALB/C nude mouse.After injecting different concentration gradient of Ad-hTERT-HSV-tk in caudal vena,the same level of GCV was peritoneal injection.The anti-tumor efficacy was analyzed by index of tumor volume,tumor weight,relative tumor curative,and tumor growth curve.Results In the presence of GCV,Ad-hTERT-HSV-tk observably inhibited growth of human prostate cancer xenografts in nude mouse in a dose dependent and there was no inhibition plateau.GCV and Ad-hTERT-HSV-tk alone caused slight inhibition of tumor growth,which was not statistically significant as compared with the negative control group（P〉0.05）.Conclusion Ad-hTERT-HSV/tk/GCV system was highly effective and safe to inhiabit the growth of human prostate cancer xenografts.And it may provide a new idea for treating human prostate cancer.