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Potent antitumor efficacy of XAF1 delivered by conditionally replicative adenovirus vector via caspase-independent apoptosis

Cancer Gene Therapy volume 14, pages 82–90 (2007)Cite this article

Abstract

XAF1 is a newly identified tumor-suppressor gene that can antagonize XIAP and sensitize cells to other cell death triggers. In this study, we utilized ZD55, a conditionally replicative adenovirus (CRAd) similar to ONYX-015 as the vector to transfer XAF1 into the tumor cells to evaluate its antitumor efficacy in vitro and in vivo. Potent and specific cytopathic effect (CPE) was observed upon infection with ZD55-XAF1 in tumor cell lines. Importantly, ZD55-XAF1 exhibited a superior suppression of tumor growth in an animal model of colorectal carcinoma in nude mice compared with Ad-XAF1 (E1-deleted replication-defective viral) and ONYX-015. Complete eradication of the established tumors was observed in four of eight mice. Our data also showed that infection with ZD55-XAF1 resulted in caspase-independent apoptosis. Although caspase-3, poly(ADP-ribose) polymerase were mildly activated in response to ZD55-XAF1 infection, pretreatment with pan-caspase inhibitor hardly influence its apoptosis-inducing activity. In summary, our study strongly suggested that ZD55-XAF1 could serve as an effective gene-virotherapy strategy and has highly potential against human cancers.

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Acknowledgements

We thank Douglas W Leaman (The University of Toledo, USA) for the provision of pcDNA3-HA-XAF1 plasmid. We also thank Lanyin Sun for help in the cell culture, Ming Zhuo and Yanhong Zhang for discussion of this paper. This work was supported by the Key Project of the Chinese Academy of Sciences (No. KSCX2-3-06), the National Natural Science Foundation of China (No. 30120160823), a Chinese National b863Q High Tech Project Foundation grant (No. 2002AA216021), the 973 Project (No. 2004CB518804).

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Authors and Affiliations

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

    R Qi, J Gu, Z Zhang, K Yang, B Li, J Fan, C Wang, Z He & X Y Liu

  2. College of Life Science & Technology, Shanghai Jiaotong University, Shanghai, China

    R Qi & Z Lin

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

    X Y Liu

  4. Division of Gastroenterology/Hepatology, Faculty of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong, China

    L Qiao

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Correspondence to X Y Liu.

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Qi, R., Gu, J., Zhang, Z. et al. Potent antitumor efficacy of XAF1 delivered by conditionally replicative adenovirus vector via caspase-independent apoptosis. Cancer Gene Ther 14, 82–90 (2007). https://doi.org/10.1038/sj.cgt.7700992

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