Local delivery of recombinant adenovirus expressing hepatitis B virus X protein and interleukin-12 results in antitumor effects via inhibition of hepatoma cell growth and intervention of tumor microenvironment

  • Authors:
    • Hong He
    • Ping Fan
    • Tao Yin
    • Qiaoling Chen
    • Huashan Shi
    • Sijia Liu
    • Haoyu Li
    • Qiuping  Jing
    • Yingying Yan
    • Hailong Zhang
    • Li Yang
    • Yanjun Wen
    • Yuhua Li
    • Ping Cheng
  • View Affiliations

  • Published online on: June 12, 2012     https://doi.org/10.3892/ijmm.2012.1027
  • Pages: 599-605
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Abstract

Hepatocellular carcinoma (HCC) is a typical hypervascular tumor. Our previous studies have demonstrated that hepatitis B virus X protein (HBx) was able to inhibit the growth of HCC cells via inducing apoptosis and inhibiting tumor angiogenesis. Interleukin-12 (IL-12) is a disulfide-linked heterodimeric cytokine with potent immunostimulatory activity and anti-angiogenic properties. In this study, to further investigate the regulatory effect of IL-12 on HBx-mediated intervention of hepatoma microenvironment especially on intervention of neovessels and immune microenvironment, we constructed the recombinant adenovirus expressing HBx and mouse IL-12 named Ad-HBx-mIL-12. HBx-mIL-12 could effectively suppress tumor growth and induce apoptosis in vivo. Moreover, treatment with Ad-HBx-mIL-12 not only induced a massive accumulation of immune cells (CD8+ T leukocytes, macrophages and dendritic cells) in tumors in situ, also apparently reduced the number of angiogenic blood vessels within tumor tissues. These results suggest that HBx-mIL-12 can not only induce cell cycle arrest and apoptosis in HCC cells, but also effectively shift the tumor microenvironment from pro-oncogenic to antitumor through recruitment of immune cells and inhibiting stromal cell growth, such as vascular endothelial cells.
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September 2012
Volume 30 Issue 3

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
He H, Fan P, Yin T, Chen Q, Shi H, Liu S, Li H, Jing Q, Yan Y, Zhang H, Zhang H, et al: Local delivery of recombinant adenovirus expressing hepatitis B virus X protein and interleukin-12 results in antitumor effects via inhibition of hepatoma cell growth and intervention of tumor microenvironment. Int J Mol Med 30: 599-605, 2012
APA
He, H., Fan, P., Yin, T., Chen, Q., Shi, H., Liu, S. ... Cheng, P. (2012). Local delivery of recombinant adenovirus expressing hepatitis B virus X protein and interleukin-12 results in antitumor effects via inhibition of hepatoma cell growth and intervention of tumor microenvironment. International Journal of Molecular Medicine, 30, 599-605. https://doi.org/10.3892/ijmm.2012.1027
MLA
He, H., Fan, P., Yin, T., Chen, Q., Shi, H., Liu, S., Li, H., Jing, Q., Yan, Y., Zhang, H., Yang, L., Wen, Y., Li, Y., Cheng, P."Local delivery of recombinant adenovirus expressing hepatitis B virus X protein and interleukin-12 results in antitumor effects via inhibition of hepatoma cell growth and intervention of tumor microenvironment". International Journal of Molecular Medicine 30.3 (2012): 599-605.
Chicago
He, H., Fan, P., Yin, T., Chen, Q., Shi, H., Liu, S., Li, H., Jing, Q., Yan, Y., Zhang, H., Yang, L., Wen, Y., Li, Y., Cheng, P."Local delivery of recombinant adenovirus expressing hepatitis B virus X protein and interleukin-12 results in antitumor effects via inhibition of hepatoma cell growth and intervention of tumor microenvironment". International Journal of Molecular Medicine 30, no. 3 (2012): 599-605. https://doi.org/10.3892/ijmm.2012.1027