【摘要】 目的:研究人端粒酶逆转录酶(hTERT)启动子调控单纯疱疹病毒胸腺嘧啶激酶(HSV-tk)基因结合环氧鸟苷(GCV)对人前列腺癌PC3、LNCaP细胞株裸鼠移植瘤的疗效。方法:建立人前列腺癌BALB/C裸鼠移植瘤模型,利用携带hTERT和HSV-tk基因的重组腺病毒Ad-hTERT-HSV-tk肿瘤局部注射荷瘤裸鼠后,腹腔注射GCV治疗。结果:(1)LNCaP细胞株、PC-3细胞株裸鼠移植瘤各组肿瘤体积的增长趋势基本一致,Ad-hTERT-HSV-tk+GCV治疗组自腹腔注射GCV后第21天开始,肿瘤体积均明显小于另3组,不同组之间,不同治疗时间差别均有统计学意义(LNCaP细胞株:F分别为17.24和557.83,P<0.01;PC-3细胞株:F分别为24.48和599.37,P<0.01),且分组和治疗时间之间存在交互作用(LNCaP细胞株:F=10.15,P<0.01;PC-3细胞株:F=11.88,P<0.01)。(2)LNCaP、PC-3细胞株移植瘤Ad-hTERT-HSV-tk/GCV治疗组凋亡率均高于其他组,而增殖都低于另3组。(3)透射电镜下发现,Ad-hTERT-HSV-tk/GCV治疗组可见凋亡小体。结论:Ad-hTERT-HSV-tk联合GCV对人前列腺癌裸鼠移植瘤模型具有明确的治疗作用。更多还原

【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 gancyclovir(GCV) in a mouse xenografts model of prostate cancer.Methods:The model of human prostate cancer xenografts was established in BALB/C nude mouse followed by local injection of Ad-hTERT-HSV-tk and peritoneal injection of GCV.The anti-tumor efficacy was evaluated by index of tumor volume.Results:In the presence of GCV,Ad-hTERT-HSV-tk effectively inhibited growth of human prostate cancer xenografts in nude mouse in both LNCaP and PC-3 groups.After 21 days,the tumor volume of Ad-hTERT-HSV-tk+ GCV group was smaller than that of other groups.Obvious necrosis and apoptosis were observed by TUNEL in Ad-hTERTHSV-tk+GCV group than those of other groups.The PCNA was lower in Ad-hTERT-HSV-tk+GCV group than that of other groups.The apoptotic body was observed by transmission electron microscope(TEM).Conclusion:The Ad-hTERT-HSV-tk+ GCV system was highly efficacious and safe to inhabit the growth of human prostate cancer xenografts,which may provide a new idea for treating human prostate cancer.更多还原