Adenoviral vector expressing CYLD augments antitumor activity of TRAIL by suppression of NF-kappa B survival signaling in hepatocellular carcinoma

	Adenoviral vector expressing CYLD augments antitumor activity of TRAIL by suppression of NF-kappa B survival signaling in hepatocellular carcinoma
	Chu, L; Gu, JF; He, ZN; Xiao, T; Liu, XY
刊名	CANCER BIOLOGY & THERAPY
	2006
卷号	5 期号:6 页码:615-622
关键词	gene therapy oncolytic adenovirus CYLD NF-kappa B TRAIL hepatocellular carcinoma
通讯作者	Liu, XY (reprint author), Inst Biochem & Cell Biol, 320 Yue Yang Rd, Shanghai 200031, Peoples R China.,xyliu@sibs.ac.cn
英文摘要	CYLD is a tumor suppressor gene related to cylindroma and is negative regulator of NF-kappa B. However, antitumor effect of CYLD has not been reported. The activation of NF-kappa B induced by tumor necrosis factor-related apoptosis-inducing ligand ( TRAIL) renders hepatocellular carcinoma (HCC) resistant to TRAIL-mediated cell apoptosis. Here we described that the adenoviral vector expressing CYLD (Ad/hTERT-CYLD) augmented the cytotoxicity of TRAIL in HCC cells by negatively regulating NF-kappa B activity since CYLD could reverse the ubiquitination of TNF receptor-associated factor 2 (TRAF2) and interact with the I kappa B kinase gamma (IKK gamma). The combined treatment of Ad/hTERT-CYLD and a conditionally replicating adenovirus carrying TRAIL gene (ZD55-TRAIL) induced rapid and potent apoptosis in HCC cells, characterized by activation of caspase-3, caspase-8, PARP and the reduction of X-linked inhibitor of apoptosis protein ( XIAP). In animal study, the combined treatment could eradicate the BEL7404 xenograft tumors. In contrast, treatment with Ad/hTERT-CYLD or ZD55-TRAIL alone achieved less antitumor effect. In conclusion: CYLD inhibits TRAIL-mediated NF-kappa B activation and enhances the sensitivity of HCC cells to TRAIL-triggered apoptosis. The combined delivery of Ad/hTERT-CYLD and ZD55-TRAIL may be a new useful strategy for HCC or other tumor cells with enhanced NF-kappa B activity.
学科主题	Oncology
类目[WOS]	Oncology
关键词[WOS]	TUMOR-NECROSIS-FACTOR ; KINASE COMPLEX ; IKK-GAMMA ; DECOY RECEPTORS ; NEMO/IKK-GAMMA ; ACTIVATION ; APOPTOSIS ; CELLS ; GENE ; INHIBITION
收录类别	SCI
语种	英语
WOS记录号	WOS:000239909500019
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/1728]
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	Chu, L,Gu, JF,He, ZN,et al. Adenoviral vector expressing CYLD augments antitumor activity of TRAIL by suppression of NF-kappa B survival signaling in hepatocellular carcinoma[J]. CANCER BIOLOGY & THERAPY,2006,5(6):615-622.
APA	Chu, L,Gu, JF,He, ZN,Xiao, T,&Liu, XY.(2006).Adenoviral vector expressing CYLD augments antitumor activity of TRAIL by suppression of NF-kappa B survival signaling in hepatocellular carcinoma.CANCER BIOLOGY & THERAPY,5(6),615-622.
MLA	Chu, L,et al."Adenoviral vector expressing CYLD augments antitumor activity of TRAIL by suppression of NF-kappa B survival signaling in hepatocellular carcinoma".CANCER BIOLOGY & THERAPY 5.6(2006):615-622.