Interferon-α enhances antitumor activities of oncolytic adenovirus-mediated IL-24 expression in hepatocellular carcinoma

Molecular Cancer

Research

Xin-Bo Xue¹  Tian-Geng You²  Zhu-Qing Zhou²  Ya-Xin Zheng²  Wei Gao²  Cong-Jun Wang²  Hui Zhang²  Chao-Wen Xiao³  Jun Chen⁴  Jia Fan⁴ 

[1]Department of Biliary and Pancreatic Surgery, Tongji hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, 430030, Wuhan, Hubei Province, China

[2]Department of General Surgery, Shanghai East Hospital, Tongji University School of Medicine, 200120, Shanghai, China

[3]Department of HBPSurgery, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, 430014, Wuhan, Hubei Province, China

[4]Liver Cancer Institute and Zhongshan Hospital, Fudan University, 200032, Shanghai, China

关键词: Gene therapy;    Hepatocellular carcinoma;    Interferon (IFN);    Mda-7/IL-24;    Nude mice;    Oncolytic adenovirus;   

DOI  :  10.1186/1476-4598-11-31

 received in 2011-11-18, accepted in 2012-05-08,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundHepatocellular carcinoma (HCC) has a dismal 5-year-survival rate of 10%, so novel strategies are warranted. IL-24 mediates anti-tumor activity reducing STAT3 expression, which suggests that interferon (IFN) alpha may augment tumor cell lysis and reduce angiogenesis. We investigated the antitumor activity of treatment with IFN-α, with the oncolytic adenovirus SG600-IL-24, or the combination of both in HCC in vitro and in vivo.ResultsRT-PCR, ELISA assay and Western-blot confirmed that the exogenous IL-24 gene was highly expressed in HCC cells infected with SG600-IL-24. Treatment with combined IFN-α and SG600-IL-24 suppressed growth and promoted apoptosis of the HepG2, MHCC97L, and HCCLM3 cell lines compared with the normal cell line L02. The combined therapy increased STAT1 and SOCS1 and apoptosis, but decreased the expression of the metastatic and angiogenic proteins MMP-2, XIAP, OPN, and VEGF, which are regulated by STAT3 in HCC cells in vitro. To assess the effects in vivo, the HCC cell line HCCLM3 was transplanted subcutaneously into the right flanks of nude mice. Mice in the IFN-α group, the SG600-IL-24 group, or the combined therapy group had significantly suppressed growth of the HCC xenografted tumors compared to the PBS control group of mice. Among the mice treated with the combination of IFN-α and SG600-IL-24, three of those eight mice had long-term survival and no evidence of a tumor. These mice also had decreased expression of the metastatic and angiogenic proteins MMP-2, XIAP, OPN, and VEGF.ConclusionsThe present study demonstrated for the first time the potential antitumor activity of IFN-α combined with the oncolytic adenovirus SG600-IL-24 in HCC both in vitro and in vivo, and suggests its further development as a potential candidate for HCC cancer gene therapy.

【 授权许可】

Unknown   
© Wang et al.; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.