田大伟, 陈业刚, 张 勇①, 王亚轩①, 黎玮①. hTERT 启动子调控腺病毒介导的HSV-TK/GCV基因系统治疗肾癌的动物实验研究[J]. 中国肿瘤临床, 2010, 37(15): 846-849. DOI: 10.3969/j.issn.1000-8179.2010.15.002
引用本文: 田大伟, 陈业刚, 张 勇①, 王亚轩①, 黎玮①. hTERT 启动子调控腺病毒介导的HSV-TK/GCV基因系统治疗肾癌的动物实验研究[J]. 中国肿瘤临床, 2010, 37(15): 846-849. DOI: 10.3969/j.issn.1000-8179.2010.15.002
shu
TIAN Dawei1, CHEN Yegang1, ZHANG Yong2, WANG Yaxuan2, LI Wei2. In Vivo Study on the Treatment of Human Renal Carcinoma by hTERT Promoter Controlled Ad-HSV-Tk/GCV Suicide Gene System[J]. CHINESE JOURNAL OF CLINICAL ONCOLOGY, 2010, 37(15): 846-849. DOI: 10.3969/j.issn.1000-8179.2010.15.002
Citation: TIAN Dawei1, CHEN Yegang1, ZHANG Yong2, WANG Yaxuan2, LI Wei2. In Vivo Study on the Treatment of Human Renal Carcinoma by hTERT Promoter Controlled Ad-HSV-Tk/GCV Suicide Gene System[J]. CHINESE JOURNAL OF CLINICAL ONCOLOGY, 2010, 37(15): 846-849. DOI: 10.3969/j.issn.1000-8179.2010.15.002
shu

hTERT 启动子调控腺病毒介导的HSV-TK/GCV基因系统治疗肾癌的动物实验研究

In Vivo Study on the Treatment of Human Renal Carcinoma by hTERT Promoter Controlled Ad-HSV-Tk/GCV Suicide Gene System

    摘要
  • 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（herpes simplex 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1.0×109pfu/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，值得进一步临床研究。

     

    Abstract: 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 line786 -0 xeno-grafts 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 × 109 pfu/kg. Then measured tumor size and tumor weight every 5 days. After 30days, 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 line786 -0 xeno-grafts 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 inhi-bition of tumor growth, but this was not statistically significant as compared to the negative control group (P>0.05). The tu -mor volume and weight were significantly smaller than the negative group and single therapy group (P<0.05). The prolifera -tion 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 pro-longed mice survival time were observed in renal carcinoma xenografts in vivo. This system did not damage normal tissue. These findings indicate that Ad-hTERT-HSV-TK/GCV system is safe, effective and highly specific. The results presented here are encouraging and will lead to a further clinical evaluation of the potential therapeutic benefits of this strategy.

     

    • HTML全文
    • 参考文献(0)
    • 相关文章
    • 施引文献
  • 资源附件(0)

/

返回文章
返回