Malignant potential of H22 hepatocarcinoma cells increases after recovery from IFN-γ-mediated inhibition

Authors

  • Wei Gong,

    1. Department of Oncology, Xiangfan Hospital Xiangfan Central Hospital, Tongji Medical College, Huazhong University of Science and Technology, Xiangfan 441021, Peoples Republic of China
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  • Ke-Zhong Ma,

    1. Department of Cardiology, Xiangfan Hospital Xiangfan Central Hospital, Tongji Medical College, Huazhong University of Science and Technology, Xiangfan 441021, Peoples Republic of China
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  • Xinjun Liang,

    1. Department of Orthopaedics, SunYatSen Memorial Hospital, SunYatSen University, Guangzhou 510120, Peoples Republic of China
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  • YanYan Liu,

    1. Department of Orthopaedics, SunYatSen Memorial Hospital, SunYatSen University, Guangzhou 510120, Peoples Republic of China
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  • Qing Zhou,

    1. Department of Pharmacy, Wuhan Central Hospital, Wuhan 430014, Peoples Republic of China
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  • JiuLiang Zhang,

    1. College of Food Science and Technology, Huazhong Agricultural University, Wuhan, Hubei 430070, Peoples Republic of China
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  • HuaiYun Chen,

    1. Department of Oncology, Xiangfan Hospital Xiangfan Central Hospital, Tongji Medical College, Huazhong University of Science and Technology, Xiangfan 441021, Peoples Republic of China
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  • Wen-Wei Liu

    Corresponding author
    1. Department of Cardiology, Xiangfan Hospital Xiangfan Central Hospital, Tongji Medical College, Huazhong University of Science and Technology, Xiangfan 441021, Peoples Republic of China
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To whom correspondence should be addressed (email yuwuheng82@163.com).

Abstract

IFN-γ (interferon γ) can effectively suppress tumours, but it has also been found to promote tumour progression. However, the underlying mechanisms by which it enhances malignancy have not been fully elucidated. By using a mouse model that expresses IFN-γ locally in muscle, we found that the growth potential of tumours was increased after a quick decrease of IFN-γ. Furthermore, the up-regulation of IRF-2 (IFN regulatory factor 2) and down-regulation of IRF-1 were also found in the tumour cells. Along these lines, IFN-γ led to down-regulated expression of cyclin-D1, Bcl-2 and Bcl-xL and up-regulated expression of p21WAF1 and Bax in tumour cells. Yet, the expression of these genes, as well as activation of ERK (extracellular signal-regulated kinase) and NF-κB (nuclear factor-κB), was also reversed shortly after a decrease in IFN-γ, all of which resulted in increase tumour cell proliferation and apoptosis resistance. These findings indicate that the malignant potential of tumour cells may be suppressed by interfering with IRF-2 signalling pathways during and after decreased IFN-γ in tumour microenvironments.

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