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E2F Promoter-Regulated Oncolytic Adenovirus with p16 Gene Induces Cell Apoptosis and Exerts Antitumor Effect on Gastric Cancer

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An Erratum to this article was published on 08 May 2009

Abstract

Replication-competent adenovirus (RCAd) constitutes an alternative in cancer therapy. For obtaining advanced RCAd generations with high oncolytic capability and a good safety profile, we constructed an E2F promoter-regulated RCAd carrying p16 gene, AdE2F-p16, in which the E1a gene was controlled by the E2F promoter. The experimental data showed that the E2F promoter endowed AdE2F-p16 with high specificity in cancer cells. While rarely replicating in normal cells, AdE2F-p16 could replicate in p16-deficient cancer cells, with 2,937- to 160,000-fold increased replicative capability in different cancer cell lines. AdE2F-p16 expressed p16 within cancer cells and led to potent antitumor efficacy in gastric cancer xenografts in nude mice, with a tumor inhibition rate of 59.14%. Due to the combined effects of cancer cell apoptosis induced by p16 expression and oncolysis by virus replication, the E2F promoter-regulated, p16-armed RCAd provides a promising strategy for cancer gene therapy.

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Acknowledgments

This work was supported by grants from the National Natural Scientific Foundation of China (No. 30572149) and the Scientific and Technological Project of Zhejiang Province, China (No. 2006C30021).

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Authors and Affiliations

  1. Department of Internal Medicine, 117 Hospital of Chinese People’s Liberation Army, Hangzhou, People’s Republic of China

    J. Ma, W. Wang, H. Hu & J. Shi

  2. Department of Gastroenterology, Jinling Hospital, Nanjing, People’s Republic of China

    X. He

  3. Laboratory of Gene & Viral Therapy, Eastern Hepatobiliary Surgical Hospital, Second Military Medical University, Shanghai, People’s Republic of China

    Y. Huang, L. Chen, W. Cong, L. Li & C. Su

  4. Shanghai SLAC Laboratory Animal Co. Ltd., Chinese Academy of Sciences - Shanghai Branch, Shanghai, 200031, China

    J. Gu

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  1. J. Ma
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Correspondence to C. Su.

Additional information

Jumin Ma and Xiaoping He contributed equally to this work.

An erratum to this article can be found at http://dx.doi.org/10.1007/s10620-009-0827-z

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Ma, J., He, X., Wang, W. et al. E2F Promoter-Regulated Oncolytic Adenovirus with p16 Gene Induces Cell Apoptosis and Exerts Antitumor Effect on Gastric Cancer. Dig Dis Sci 54, 1425–1431 (2009). https://doi.org/10.1007/s10620-008-0543-0

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