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Potent antitumor activity of oncolytic adenovirus-mediated SOCS1 for hepatocellular carcinoma

Gene Therapy volume 20, pages 84–92 (2013)Cite this article

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Abstract

Signal transducer and activator of transcription 3 (STAT3) is constitutively activated in diverse cancers, which contributes to the proliferation and survival of cancer cells by upregulating apoptosis inhibitors and cell cycle regulators. Suppressor of cytokine signaling 1 (SOCS1) is an important negative regulator of STAT pathways and is frequently silenced in many types of cancers. In this study, we used oncolytic adenoviral vector to deliver SOCS1 gene (AdCN305-SOCS1) to treat hepatocellular carcinoma (HCC). Our data showed that SOCS1 was downregulated in HCC cells by hypermethylation. AdCN305-SOCS1 was found selectively replicated, which led to SOCS1 overexpression in HCC cells. Infection of HCC cells with AdCN305-SOCS1 resulted in inhibition of STAT3 phosphorylation and downregulation of survivin, cyclin D1, Bcl-xL and C-myc. AdCN305-SOCS1 exhibited strong cytotoxicity to HCC cells by inducing apoptosis in vitro and in vivo. This study suggests that transfer of SOCS1 by an oncolytic adenovirus may be a potent antitumor approach for cancer therapy.

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Acknowledgements

This work was supported by funds from National Natural Sciences Foundation of China (30872984) and National Basic Research Program of China (973 Program, No. 2010CB529406).

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  1. L Liu and W Li: These authors contributed equally to this work.

Authors and Affiliations

  1. Xinyuan Institute of Medicine and Biotechnology, School of Life Sciences, Zhejiang Sci-Tech University, Hangzhou, Zhejiang, China

    L Liu, W Li, X Wei, Q Cui, W Lou, G Wang, X Hu & C Qian

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  1. L Liu
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Correspondence to C Qian.

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Liu, L., Li, W., Wei, X. et al. Potent antitumor activity of oncolytic adenovirus-mediated SOCS1 for hepatocellular carcinoma. Gene Ther 20, 84–92 (2013). https://doi.org/10.1038/gt.2012.4

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