Zhang et al. Journal of Experimental & Clinical Cancer Research 2010, 29:52 http://www.jeccr.com/content/29/1/52 R E S E A R C H RPeoseatrechnt anti-tumor activity of telomerase-dependent and HSV-TK armed oncolytic adenovirus for non-small cell lung cancer in vitro and in vivo Ju-Feng Zhang1,2, Fang Wei1, Hui-Ping Wang1, Hui-Ming Li1, Wei Qiu1, Peng-Kang Ren1, Xia-Fang Chen1 and Qian Huang*1 Open Access Abstract Background: 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. Methods: 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'. Results: 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. Conclusion: The results from this study showed that Ad.hTERT-E1A-TK/GCV could be a potent but safe anti-tumor strategy for NSCLC biotherapy. Background Lung cancer is one of the most common malignant neo- plasm diseases in which non-small cell lung cancer (NSCLC) constitutes 80%-85% of all lung cancers [1]. Due to the lack of early diagnostic methods, most of NSCLC cases are diagnosed at the late phase and patients usually lose the opportunity of surgical treatment. Despite the fact that chemotherapy and radiotherapy provides many options to treat NSCLC, a survival plateau has been reached and its mortality is still in the first place in cancer patients [2,3]. Therefore it is urgent to explore other treatment strategies. Molecule targeting therapy repre- * Correspondence: qhuang@sjtu.edu.cn 1 Central Experimental Laboratory, First People's Hospital, Shanghai Jiaotong University, 85 Wujin Road, Shanghai 200080, PR China Full list of author information is available at the end of the article sents a rapidly growing cancer treatment strategy and several drugs have been proven effective in many preclin- ical and clinical setting [4,5]. Suicide gene therapy pos- sesses the advantage of molecule targeting strategies because the suicide gene functions in the transformed tumor cells and then selectively kills transformed tumor cells and their surrounding cells via bystander effects. In some extent, the suicide gene therapy could overcome the systemic toxicity of conventional chemotherapy. Herpes Simplex Virus Thymidine Kinase/gancyclovir (HSV-TK/ GCV) is one of the most frequently utilized forms of sui- cide gene therapy. HSV-TK can catalyze GCV into mono- phosphorylated GCV (GCV-MP) that will then be converted into toxic gancyclovir triphosphate (GCV-TP) by other cellular kinases and thereafter cause cell growth inhibition or initiates cell death. According to previous © 2010 Zhang et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons BioMed Central Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.