Zhao Zhen, Huang Rui, Cai Huawei, Liu Bin, Zeng Yu, Kuang Anren
Department of Nuclear Medicine, West China Hospital of Sichuan University Chengdu, Sichuan Province, China.
Int J Clin Exp Pathol. 2017 Nov 1;10(11):11037-11043. eCollection 2017.
Currently, the intratumoral (i.t.) injection of adenovirus-mediated cancer gene therapy has been reported in numerous investigations. However, the intravenous (i.v.) injection of adenovirus is more suited for disseminated tumors and distant metastatic lesions. The survivin promoter, which has tumor-selective capability, was used to construct an adenoviral vector, and its feasibility to carry the sodium iodide symporter (NIS) gene for potential tumor-targeting transfection into carcinoma was evaluated in this study. An in vitro cellular assay using HepG2 hepatocellular carcinoma (HCC) cells exhibited iodide uptake after infection with Ad-Sur-NIS, and the uptake reached a maximum level at 30 min. The effective half-life of I efflux from Ad-Sur-NIS infected HepG2 cells was 16.67 ± 1.08 min. Moreover, in vivo transfection of Ad-Sur-NIS via i.v. injection induced more effective transfection and, accordingly, induced higher uptake of pertechnetate in HCC xenograft tumors than did the non-specific transfection of Ad-CMV-NIS (i.v.) (P<0.05), indicating possible selective NIS gene-transfecting image strategies by the survivin promoter.
目前,在众多研究中已报道了腺病毒介导的癌症基因疗法的瘤内(i.t.)注射。然而,腺病毒的静脉内(i.v.)注射更适用于播散性肿瘤和远处转移病灶。具有肿瘤选择性能力的生存素启动子被用于构建腺病毒载体,并且在本研究中评估了其携带碘化钠同向转运体(NIS)基因用于潜在肿瘤靶向转染至癌组织的可行性。使用HepG2肝细胞癌(HCC)细胞进行的体外细胞试验显示,感染Ad-Sur-NIS后细胞摄取碘,且摄取在30分钟时达到最高水平。Ad-Sur-NIS感染的HepG2细胞中碘流出的有效半衰期为16.67±1.08分钟。此外,通过静脉内注射Ad-Sur-NIS进行体内转染比Ad-CMV-NIS(静脉内)的非特异性转染诱导了更有效的转染,因此在HCC异种移植瘤中诱导了更高的高锝酸盐摄取(P<0.05),表明生存素启动子可能具有选择性NIS基因转染成像策略。