摘要
目的：探讨带有人端粒酶逆转录酶（Human Telomerase Reverse Transcriptase，hTERT）启动子驱动单纯疱疹病毒胸腺嘧啶激酶（herpessimplex virus—thymidine kinase，HSV—TK）基因的重组腺病毒（Ad—TK）结合无毒的环氧鸟苷（gancyclovir，GCV）对人肾细胞癌的治疗作用。方法：建立人肾细胞癌移植瘤裸鼠模型，采用hTERTp为启动子驱动Ad—HSV-TK尾静脉注射荷瘤小鼠，注射剂量1．0×10^9pfu／kg，腹腔注射GCV，每5天测量移植瘤体积和重量，30天后处死裸鼠，观察肿瘤体积、相对肿瘤体积、瘤重、肿瘤增殖率及检测凋亡率，评价Ad—hTERT—HSV-TK/GCV的抗肿瘤活性，并与Ad—hTERT—HSV—TK和GCV单独治疗比较。结果：成功建立肾细胞癌移植瘤裸鼠模型。Ad—hTERT—HSV—TK/GCV对裸鼠移植瘤生长具有明显抑制作用，对心、肺、肝、脑、肾、脾无明显损害。而Ad—hTERT-HSV-TK和GCV单独治疗组虽然能抑制肿瘤生长，但是较阴性对照组无明显统计学差异。Ad—hTERT-HSV-TK／GCV治疗组的移植瘤体积、重量都明显小于阴性对照组、Ad—TK和GCV治疗组（P〈0．05）；Ad—hTERT-HSV-TK／GCV治疗组的凋亡指数为（3．2±0．3）％，其他组凋亡指数分别是（0．1±0．1）％，（0．2±0．1）％，（0．2±0．1）％，与Ad—hTERT—HSV—TK/GCV治疗组相比差异具有显著性（P〈0．05）；免疫组化检测结果显示Ad—hTERT—HSV—TK／GCV治疗组的增殖指数为（27．57±9．36）％，而其他组的增殖指数则分别为（71．2±13．1）％．（69．8±11．6）％，（72．4±12．3）％，Ad—hTERT—HSV—TK／GCV治疗组同其他组相比差异具有显著性（P〈0．01）。结论：Ad—hTERT—HSV—TK／GCV对肾细胞癌具有明确的抑制肿瘤生长促进肿瘤凋亡及提高存活率的作用，且对正常组织无明显损伤；Ad—hTERT—HSV—TK／GCV系统是一种安全有效且靶向性高的基因疗法，值得进一�
Objective： To investigate the efficacy of replication-deficient adenovirus carrying the HSV-TK gene under the control of the human telomerase reverse transcriptase （hTERT） promoter and ganciclovir （GCV） in a mouse xenograft model of renal carcinoma. Methods： Researchers established the model of human renal carcinoma cell line 786-0 xenografts in BALB/C nude mice and administered peritoneal injections of GCV and tail vein injections of Ad-hTERT-HSV-TK at the dose of 1.0× 10^9 pfu/kg. Then measured tumor size and tumor weight every 5 days. After 30 days, all nude mice were killed and all tumors were completely resected. Then the antitumor efficacy was evaluated by relative tumor volume, tumor weight, tumor proliferation and tumor apoptosis. All these factors were compared with those of the negative control group and single therapy group. Results： This study has established the model of human renal carcinoma cell line 786-0 xenografts in BALB/C nude mice successfully. The Ad-hTERT-HSV-TK GCV system could suppress tumor growth in nude mice more effectively while having no significant damage to heart, lung, liver, brain and spleen. Ad-TK or GCV alone caused inhibition of tumor growth, but this was not statistically significant as compared to the negative control group （P〉0.05）. The tumor volume and weight were significantly smaller than the negative group and single therapy group （P〈0.05）. The proliferation index of the Ad-hTERT-HSV-TK/GCV group was 3.2±0.3（%）,while other groups were 0.1±0.1（%）,0.2±0.1 （%）, 0.2±0.1 （%）, respectively, the difference was statistically significant （P〈0.05）. The apoptosis index of the Ad-hTERT-HSV-TK/GCV group was 27.57±9.36（%）,while other groups were 71.2±13.1（%）, 69.8±11.6（%）, 72.4±12.3（%）, respectively, the difference was statistically significant （P〈0.01）. Conclusion： Significant inhibition of tumor proliferation,promotion of apoptosis and prolonged mice survival time were observed in renal carcinoma xeno
出处
《中国肿瘤临床》
CAS
CSCD
北大核心
2010年第15期846-849,共4页
Chinese Journal of Clinical Oncology
