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Gene-viro-therapy targeting liver cancer by a dual-regulated oncolytic adenoviral vector harboring IL-24 and TRAIL

Cancer Gene Therapy volume 19, pages 49–57 (2012)Cite this article

Abstract

Cancer-targeting gene-viro-therapy is a promising cancer therapeutic strategy that strengthens the antitumor effect of oncolytic viruses by expressing an inserted foreign antitumor gene. To achieve liver cancer targeting and to improve the safety of the ZD55 vector (a widely-used E1B55KD gene-deleted oncolytic adenoviral vector (OV), we previously constructed), we designed a novel OV named Ad·AFP·D55 that selectively replicates in hepatocellular carcinoma (HCC) cells by replacing the E1A promoter with the liver-cancer specific α-Fetoprotein (AFP) promoter based on the ZD55 vector. We found that the oncolytic adenoviruses Ad·AFP·D55-IL-24 and Ad·AFP·D55-TRAIL express tumor-suppressor gene interleukin-24 (IL-24) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), respectively, significantly suppressed the HCC cell growth in vitro by inducing apoptosis by the caspase-8 and mitochondria-dependent caspase-9 signaling pathways. Furthermore, the combined treatment of Ad·AFP·D55-IL-24 and Ad·AFP·D55-TRAIL showed strong antitumor effects in vivo by significantly inhibiting the tumor growth in HCC HuH-7 cell xenograft mice, and markedly increasing animal survival rate. Therefore, this novel HCC cell-targeting OV carrying tumor-suppressor genes may provide a promising approach for liver cancer gene therapy.

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Acknowledgements

We wish to thank Ying Xu, Lanying Sun, Jingfa Gu, and Cell Analysis Center (Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences) for the professional technical assistance, and Mitchell Sullivan (University of Queensland) for proof-reading the article. This work was supported by the National Basic Research Program of China (973 Program) (No. 2010CB529901), Important National Science & Technology Specific Project of Hepatitis and Hepatoma Related Program (2008ZX10002-023), New Innovation Program (2009-ZX-09102-246), the Natural Science Foundation of China (Nos. 30801445, 81172971 & 30970607) and the Zhejiang Sci-Tech University grant (1016834-Y).

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Authors and Affiliations

  1. Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan, China

    X Liu & K Huang

  2. Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China

    X Liu, X Cao, R Wei, Y Cai, H Li, J Gui, D Zhong & X-Y Liu

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  1. X Liu
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Correspondence to X-Y Liu or K Huang.

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Liu, X., Cao, X., Wei, R. et al. Gene-viro-therapy targeting liver cancer by a dual-regulated oncolytic adenoviral vector harboring IL-24 and TRAIL. Cancer Gene Ther 19, 49–57 (2012). https://doi.org/10.1038/cgt.2011.67

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