Suppression of tumor growth by oncolytic adenovirus-mediated delivery of an antiangiogenic gene, soluble Flt-1

	Suppression of tumor growth by oncolytic adenovirus-mediated delivery of an antiangiogenic gene, soluble Flt-1
	Zhang, ZL; Zou, WG; Wang, JH; Gu, JF; Dang, YK; Li, BH; Zhao, LL; Qian, C; Qian, QJ; Liu, XY
刊名	MOLECULAR THERAPY
	2005
卷号	11 期号:4 页码:553-562
关键词	oncolytic adenovirus E1B-55-kDa gene antiangiogenesis sflt-1(1-3) gene gene-viral therapy
通讯作者	Liu, XY (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, 320 Yue Yang Rd, Shanghai 200031, Peoples R China.,xyliu@sibs.ac.cn
英文摘要	Armed oncolytic adenoviruses represent an appealing tumor treatment approach, as they can attack tumors at multiple levels. In this study, considering that angiogenesis plays a central role in tumor growth, we inserted an antiangiogenic gene, sflt-7(1-3) (the first three extracellular domains of FLT1, the hVEGF receptor-1), into an E1B-55-kDa-deleted oncolytic adenovirus (ZD55) to construct ZD55-sflt-1. Although soluble (s) Flt-1 did not affect tumor cell growth, ZD55-sflt-1 could specifically induce a cytopathic effect in tumor cells, like ONYX-015. The secretion of sFlt-1 from ZD55-sflt-1 was much higher than that from replication-deficient Ad-sflt-1 upon infection of SW620 human colon tumor cells, leading to a stronger inhibitory effect on VEGF-induced proliferation and tube formation ability of HUVECs. Moreover, marked reduction of tumor growth and long-term survival rates were observed in ZD55-sflt-1-treated nude mice with subcutaneous SW620 tumor. Its efficacy correlated with a decrease in microvessel density and an increase in apoptotic tumor cells. In addition, ZD55-sflt-1 showed a synergic effect with the chemotherapeutic agent 5-FU. These results indicate that ZD55-sflt-1, combining the advantages of oncolytic adenovirus and antiangiogenic gene therapy, is a powerful agent for human tumor treatment.
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]	FACTOR RECEPTOR ; REPLICATING ADENOVIRUS ; COMPETENT ADENOVIRUS ; EXTRACELLULAR DOMAIN ; ANTITUMOR EFFICACY ; CANCER-THERAPY ; P53 STATUS ; IN-VIVO ; ANGIOGENESIS ; CELLS
收录类别	SCI
语种	英语
WOS记录号	WOS:000227991700010
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/1900]
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	Zhang, ZL,Zou, WG,Wang, JH,et al. Suppression of tumor growth by oncolytic adenovirus-mediated delivery of an antiangiogenic gene, soluble Flt-1[J]. MOLECULAR THERAPY,2005,11(4):553-562.
APA	Zhang, ZL.,Zou, WG.,Wang, JH.,Gu, JF.,Dang, YK.,...&Liu, XY.(2005).Suppression of tumor growth by oncolytic adenovirus-mediated delivery of an antiangiogenic gene, soluble Flt-1.MOLECULAR THERAPY,11(4),553-562.
MLA	Zhang, ZL,et al."Suppression of tumor growth by oncolytic adenovirus-mediated delivery of an antiangiogenic gene, soluble Flt-1".MOLECULAR THERAPY 11.4(2005):553-562.