Central Experimental Laboratory, First People's Hospital, Shanghai Jiaotong University, Shanghai 200080, PR China.
J Exp Clin Cancer Res. 2010 May 20;29(1):52. doi: 10.1186/1756-9966-29-52.
Non-small cell lung cancer (NSCLC) is the leading cause of cancer related mortality, any improvements in therapeutic strategies are urgently required. In this study we generated a novel 'suicide gene' armed oncolytic adenoviral vector and investigated its antitumor effect both in vitro and in vivo.
Since the up-regulated expression of human telomerase reverse transcriptase (hTERT) is a hallmark of alltypes of NSCLC, we chose hTERT promoter to transcriptionally control E1A gene expression to obtain adenoviral replication in NSCLC. In order to further enhance anti-tumor effect of this oncolytic adenoviral vector, we inserted a 'suicide gene' i.e. Herpes Simplex Virus Thymidine Kinase (HSV-TK) into oncolytic adenoviral vector to engineer a novel armed oncolytic adenoviral vector 'Ad.hTERT-E1A-TK'.
Ad.hTERT-E1A-TK efficiently killed different types of tumor cells including two types of NSCLC cells in vitro, causing no damage to normal primary fibroblasts. Furthermore, Ad.hTERT-E1A-TK infection combined with administration of prodrug gancyclovir (GCV) resulted in more potent cytotoxicity on NSCLC cells, and synergistically suppressed human NSCLC tumor growth in nude mice.
The results from this study showed that Ad.hTERT-E1A-TK/GCV could be a potent but safe anti-tumor strategy for NSCLC biotherapy.
非小细胞肺癌（NSCLC）是癌症相关死亡的主要原因，迫切需要改进治疗策略。在这项研究中，我们生成了一种新型的“自杀基因”武装溶瘤腺病毒载体，并在体外和体内研究了其抗肿瘤作用。
由于人端粒酶逆转录酶（hTERT）的上调表达是所有类型 NSCLC 的标志，我们选择 hTERT 启动子来转录控制 E1A 基因的表达，以在 NSCLC 中获得腺病毒复制。为了进一步增强这种溶瘤腺病毒载体的抗肿瘤效果，我们将“自杀基因”即单纯疱疹病毒胸苷激酶（HSV-TK）插入溶瘤腺病毒载体中，构建了一种新型武装溶瘤腺病毒载体“Ad.hTERT-E1A-TK”。
Ad.hTERT-E1A-TK 在体外有效杀死了不同类型的肿瘤细胞，包括两种类型的 NSCLC 细胞，对正常原代成纤维细胞没有损伤。此外，Ad.hTERT-E1A-TK 感染联合使用前药更昔洛韦（GCV）对 NSCLC 细胞产生更强的细胞毒性作用，并协同抑制裸鼠人 NSCLC 肿瘤生长。
这项研究的结果表明，Ad.hTERT-E1A-TK/GCV 可能是 NSCLC 生物治疗的一种有效且安全的抗肿瘤策略。
