Sign up for Table of Contents Alerts.
Email this page
Print this page
Research Paper
Adenoviral Vector Expressing CYLD Augments Antitumor activity of TRAIL by Suppression of NF-κB Survival Signaling in Hepatocellular Carcinoma
Liang Chu, Jinfa Gu, Zhongniu He, Tian Xiao and Xinyuan Liu
volume 5 | issue 6
june 2006Pages: 615-622
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDFIf the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.
CYLD is a tumor suppressor gene related to cylindroma and is negative regulator of NF-κB. However, antitumor effect of CYLD has not been reported. The activation of NF-κB 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-κB activity since CYLD could reverse the ubiquitination of TNF receptor-associated factor 2 (TRAF2) and interact with the I B kinase? (IKKγ). 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-κB 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-κB activity.
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDFIf the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.