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Adenovirus-mediated HCCS1 overexpression elicits a potent antitumor efficacy on human colorectal cancer and hepatoma cells both in vitro and in vivo

Cancer Gene Therapy volume 15, pages 808–816 (2008)Cite this article

Abstract

We had characterized earlier the novel tumor suppressor gene hepatocellular carcinoma suppressor 1 (HCCS1), and demonstrated that expression of exogenous HCCS1 gene in human hepatocarcinoma cells could remarkably suppress their abilities to develop tumors in nude mice and to form colonies in soft agar. In this study, we provide further experimental evidence to confirm the role of HCCS1 as a tumor suppressor gene and investigate its potential in therapeutic applications by using adenovirus vectors. We show that HCCS1 overexpression, mediated by replication-deficient adenovirus, significantly suppressed the growth of human colorectal cancer cells, as well as hepatocellular carcinoma cells in vitro and in vivo. To further improve its antitumor efficacy, we inserted the HCCS1 gene into an oncolytic adenovirus. This HCCS1-armed oncolytic adenovirus exhibited a dramatic inhibitory effect on cancer cells in vitro and in vivo, and led to a complete regression of 50% of established tumor xenografts in nude mice. Taken together, our data suggest that HCCS1 is a promising therapeutic gene for the treatment of human cancers.

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Acknowledgements

We thank Lanying Sun for her excellent technical assistance in cell culture, and Dr Yiping Jing and Dr Yangxin Zhao for the discussion. This work was supported by the grants from the Key Programs of the National Natural Science Foundation of China (No. 30330350), Hi-Tech Research Development Program of China (863 Program, No. 2007AA021006), the Key Project of the Chinese Academy of Sciences (No. KSCX2-YW-R-09), and Shanghai Committee of Science and Technology (No. 04XD14015).

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Author notes

  1. Y Gan, J Gu and X Cai: These authors contributed equally to this work.

Authors and Affiliations

  1. Laboratory for Cellular and Molecular Immunology, Shanghai Cancer Institute, Shanghai, China

    Y Gan, X Cai, J Hu & X Zhao

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

    J Gu & X Y Liu

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

    X Y Liu

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  1. Y Gan
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  3. X Cai
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  4. J Hu
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  5. X Y Liu
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Correspondence to X Y Liu or X Zhao.

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Gan, Y., Gu, J., Cai, X. et al. Adenovirus-mediated HCCS1 overexpression elicits a potent antitumor efficacy on human colorectal cancer and hepatoma cells both in vitro and in vivo. Cancer Gene Ther 15, 808–816 (2008). https://doi.org/10.1038/cgt.2008.52

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