A survivin-mediated oncolytic adenovirus induces non-apoptotic cell death in lung cancer cells and shows antitumoral potential in vivo

	A survivin-mediated oncolytic adenovirus induces non-apoptotic cell death in lung cancer cells and shows antitumoral potential in vivo
	Li, BH; Liu, XR; Fan, JK; Qi, R; Bo, LN; Gu, JF; Qian, QJ; Qian, C; Liu, XY
刊名	JOURNAL OF GENE MEDICINE
	2006
卷号	8 期号:10 页码:1232-1242
关键词	oncolytic adenovirus survivin promoter non-apoptotic cell death
通讯作者	Liu, XY (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Shanghai 200031, Peoples R China.,xyliu@sibs.ac.cn
英文摘要	Background Conditionally replicating adenoviruses or oncolytic adenoviruses, which can replicate selectively in tumor cells and kill them, represent an innovative class of promising cancer therapeutics. Survivin is the smallest member of the inhibitor of apoptosis (IAP) family, which is transcriptionally upregulated exclusively in most malignant tissues but not in normal tissues. It has been reported that activity of the survivin promoter is tumor-specific, which makes the survivin promoter a good candidate to construct oncolytic viral vectors. Methods A luciferase reporter assay was used to determine the activity of the survivin promoter in tumor and normal cells. An oncolytic adenovirus (Ad.SP/E1A) was generated by homologous recombination. The oncolytic efficacy of Ad.SP/E1A was evaluated in cell lines and in a human lung xenograft tumor mouse model. Results Survivin expression was highly upregulated in tumor cells both at the protein and mRNA level. The luciferase reporter assay showed that survivin promoter activity is tumor-specific. Ad.SP/E1A expressed E1A selectively in tumor cells and induced cytotoxicity, but not in normal cells. Moreover, in animal experiments, intratumoral administration of Ad.SP/E1A significantly suppressed the growth of xenograft tumors. Further investigation showed that Ad.SP/E1A induced cell death by an apoptosis-independent pathway. Conclusions Ad.SP/E1A could be a potent therapeutic agent for cancer gene therapy. The investigation of the mechanisms of oncolytic virus-induced cell death in this work will shed light on the construction of more powerful vectors for cancer therapy. Copyright (c) 2006 John Wiley & Sons, Ltd.
学科主题	Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine
类目[WOS]	Biotechnology & Applied Microbiology ; Genetics & Heredity ; Medicine, Research & Experimental
关键词[WOS]	CONDITIONALLY REPLICATING ADENOVIRUS ; GENE-EXPRESSION ; VIRAL REPLICATION ; TUMOR-CELLS ; PROMOTER ; THERAPY ; SELECTIVITY ; INHIBITION ; ACTIVATION ; INDUCTION
收录类别	SCI
语种	英语
WOS记录号	WOS:000242030000004
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/1766]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Li, BH,Liu, XR,Fan, JK,et al. A survivin-mediated oncolytic adenovirus induces non-apoptotic cell death in lung cancer cells and shows antitumoral potential in vivo[J]. JOURNAL OF GENE MEDICINE,2006,8(10):1232-1242.
APA	Li, BH.,Liu, XR.,Fan, JK.,Qi, R.,Bo, LN.,...&Liu, XY.(2006).A survivin-mediated oncolytic adenovirus induces non-apoptotic cell death in lung cancer cells and shows antitumoral potential in vivo.JOURNAL OF GENE MEDICINE,8(10),1232-1242.
MLA	Li, BH,et al."A survivin-mediated oncolytic adenovirus induces non-apoptotic cell death in lung cancer cells and shows antitumoral potential in vivo".JOURNAL OF GENE MEDICINE 8.10(2006):1232-1242.