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

He,Hong; Fan,Ping; Yin,Tao; Chen,Qiaoling; Shi,Huashan; Liu,Sijia; Li,Haoyu; Jing,Qiuping; Yan,Yingying; Zhang,Hailong; Yang,Li; Wen,Yanjun; Li,Yuhua; Cheng,Ping

doi:10.3892/ijmm.2012.1027

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
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Affiliations: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan, P.R. China, School of Life Science, Sichuan University, Chengdu, Sichuan, P.R. China
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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