Augmenting the Antitumor Effect of TRAIL by SOCS3 with Double-Regulated Replicating Oncolytic Adenovirus in Hepatocellular Carcinoma

	Augmenting the Antitumor Effect of TRAIL by SOCS3 with Double-Regulated Replicating Oncolytic Adenovirus in Hepatocellular Carcinoma
	Wei, RC; Cao, X; Gui, JH; Zhou, XM; Zhong, D; Yan, QL; Huang, WD; Qian, QJ; Zhao, FL; Liu, XY
刊名	HUMAN GENE THERAPY
	2011
卷号	22 期号:9 页码:1109-1119
通讯作者	Liu, XY (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Mol Cell Biol Lab, 320 Yueyang Rd, Shanghai 200031, Peoples R China.,zhaof4731@163.com ; xyliu@sibs.ac.cn
英文摘要	Aberrant JAK/STAT3 pathway has been reported to be related to hepatocellular carcinoma (HCC) in many cell lines. In this study, a double-regulated oncolytic adenovirus vector that can replicate and induce a cytopathic effect in alpha-fetoprotein (AFP)-positive HCC cell lines with p53 dysfunction was successfully constructed. Two therapeutic genes, suppressor of cytokine signaling 3 (SOCS3) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), were chosen and incorporated into this vector system, respectively. The combined treatment of AFP-D55-SOCS3 and AFP-D55-TRAIL (2:3 ratio) exhibited potent antitumor activity in AFP-positive HCC cell lines compared with any other treatment both in vitro and in vivo. Specific replication and low progeny yield in AFP-positive HCC cell lines rendered these double-regulated oncolytic adenoviruses remarkably safe. Our data demonstrated that restoration of SOCS3, which inhibits the JAK/STAT3 pathway, by AFP-D55-SOCS3 not only could antagonize HCC therapeutic resistance to TRAIL and adenoviruses, but could also induce cell cycle arrest in HCC cell lines. SOCS3 could down-regulate Cyclin D1 and anti-apoptotic proteins such as XIAP, Survivin, Bcl-xL, and Mcl-1, which are responsible for the synergistic inhibitory effects of AFP-D55-SOCS3 and AFP-D55-TRAIL. Dual gene and double-regulated oncolytic adenoviruses may provide safety and excellent antitumor effects for liver cancer, which is the advantage of a cancer-targeting gene virotherapy strategy.
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]	APOPTOSIS-INDUCING LIGAND ; GENE-VIROTHERAPY ; CANCER ; CELLS ; DEATH ; INHIBITION ; EXPRESSION ; RECEPTORS ; SURVIVAL ; PROTEIN
收录类别	SCI
语种	英语
WOS记录号	WOS:000295034100012
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/848]
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	Wei, RC,Cao, X,Gui, JH,et al. Augmenting the Antitumor Effect of TRAIL by SOCS3 with Double-Regulated Replicating Oncolytic Adenovirus in Hepatocellular Carcinoma[J]. HUMAN GENE THERAPY,2011,22(9):1109-1119.
APA	Wei, RC.,Cao, X.,Gui, JH.,Zhou, XM.,Zhong, D.,...&Liu, XY.(2011).Augmenting the Antitumor Effect of TRAIL by SOCS3 with Double-Regulated Replicating Oncolytic Adenovirus in Hepatocellular Carcinoma.HUMAN GENE THERAPY,22(9),1109-1119.
MLA	Wei, RC,et al."Augmenting the Antitumor Effect of TRAIL by SOCS3 with Double-Regulated Replicating Oncolytic Adenovirus in Hepatocellular Carcinoma".HUMAN GENE THERAPY 22.9(2011):1109-1119.