摘要
目的:研究人甲胎蛋白启动子控制表达HIVVpr基因的重组腺病毒对裸鼠肝癌模型的肿瘤组织生长抑制作用,探讨其应用于肝癌基因治疗的可行性。方法:将人甲胎蛋白启动子控制表达HIVVpr基因的重组腺病毒(rvAdAFP-Vpr)直接注射到利用BEL-7402细胞建立的肝癌裸鼠模型瘤体内,同时往裸鼠腹腔内注射环磷酰胺(CTX),经过1个月的治疗,利用肿瘤生长曲线、增殖指数、凋亡指数等指标,观察rvAdAFP-Vpr对肝癌组织生长抑制的效果。结果:人甲胎蛋白启动子控制表达HIVVpr基因的重组腺病毒在肝癌组织中表达了Vpr蛋白,rvAdAFP-Vpr注射明显诱导肿瘤细胞凋亡,抑制了体内肝癌组织的生长,rvAdAFP-Vpr治疗组和rvAdAFP-Vpr+CTX治疗组抑瘤率分别达到41%和66.7%,与空白对照组和rvAd-null组相比,具有统计学意义,差异显著(P<0.05,P<0.01),两组的Ki-67指数和凋亡指数相比,对照组和空腺病毒载体(rvAd-null)组同样具有统计学意义,差异显著(P<0.05,P<0.01)。结论:人甲胎蛋白启动子控制表达HIVVpr基因的重组腺病毒rvAdAFP-Vpr通过引起肝癌细胞凋亡,有效抑制了体内肝癌组织的生长。本研究结果为HIV-1Vpr应用于肝癌治疗提供了依据。
Objective:To investigate the anti - hepatic carcinoma effects of recombinant adenovirus encoding HIV Vpr gene driven by human alpha fetoprotein (AFP) promoter ( rvAdAFP - Vpr) in nude mice and discuss the feasi- bility of using the recombinant adenovirus in the gene therapy of hepatic carcinoma. MethOdS: After transplantation of BEL -7402 hepatic carcinoma ceils in the liver, nude mice were injected with rvAdAFP - Vpr into the tumor tissues. Meanwhile, cycl,-phosphamide (CTX) was intraperitoneally injected. After one month of treatment, the inhibitory effect of rvAdAFP - Vpr on the growth of hepatoma was assessed by using the tumor growth curve, proliferation index, and apoptotic index. Results: The Vpr protein was expressed in hepatic carcinoma tissue after injection of rvAdAFP - Vpr. rvAdAFP - Vpr injection significantly induced tumor cell apoptosis and suppressed the growth of hepatoma in vivo. The tumor - suppressing rate was 41% in the rvAdAFP - Vpr group and 66.7% in the rvAdAFP - Vpr + CTX group, and the rates in the two groups were significantly higher than those in the control group and the rvAd - null group ( P 〈 0.05, P 〈 0.01 ). The Ki - 67 index and the apoptotic index were also significandy higher in the rvAdAFP - Vpr and rvAdAFP - Vpr + CTX groups than those in the control and rvAd - null groups ( P 〈 0.05, P 〈 0.01 ). Conclusion : rvAdAFP - Vpr effectively suppresse the growth of hepatic carcinoma in vivo through inducing apoptosis of tumor ceils. The present study demonstrated the feasibility of using HIV - 1 - Vpr in the treatment of hepatic carcinoma.
出处
《上海医药》
CAS
2006年第7期308-312,共5页
Shanghai Medical & Pharmaceutical Journal
基金
国家自然科学基金资助项目No3000761748
关键词
重组腺病毒
肝癌
甲胎蛋白启动子
基因治疗
recombinant adenovirus
hepatoma
alpha fetoprotein promoter
gene therapy