Title |
Downregulation of A20 increases the cytotoxicity of IFN-γ in hepatocellular carcinoma cells
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Published in |
Drug Design, Development and Therapy, September 2017
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DOI | 10.2147/dddt.s135993 |
Pubmed ID | |
Authors |
Lei Yin, Zheng Fang, Ning-jia Shen, Ying-he Qiu, Ai-jun Li, Yong-jie Zhang |
Abstract |
Hepatocellular carcinoma (HCC) is a highly fatal disease mandating development of novel, effective therapeutic strategy. Interferon-gamma (IFN-γ) is a pleiotropic cytokine with immunomodulatory, antiviral, and antitumor effects. Although IFN-γ is a promising antitumor agent, its application is limited by resistance in tumor cells. A20 is a zinc-finger protein that was initially identified as a gene product induced by tumor necrosis factor α in human umbilical vein endothelial cells. In this study, we found that silencing of A20 combined with IFN-γ significantly represses cell viability, and induces apoptosis and cell-cycle arrest in HCC cells. By investigating mechanisms implicated in A20 and IFN-γ-mediated signaling pathways, we revealed that the phosphoinositide 3-kinase/Akt signaling pathway and antiapoptotic B-cell lymphoma 2 proteins were repressed. Moreover, we also found that phosphorylation of STAT1 and STAT3 was significantly enhanced after the downregulation of A20 in combination with treatment of IFN-γ. Inhibitor of STAT1 but not STAT3 could block the antitumor effect of IFN-γ. Therefore, targeting A20 enhances the cytotoxicity of IFN-γ against HCC cells and may present a promising therapeutic strategy for HCC. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 10 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Ph. D. Student | 3 | 30% |
Student > Bachelor | 2 | 20% |
Student > Doctoral Student | 1 | 10% |
Student > Master | 1 | 10% |
Unknown | 3 | 30% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 3 | 30% |
Medicine and Dentistry | 2 | 20% |
Chemistry | 1 | 10% |
Agricultural and Biological Sciences | 1 | 10% |
Unknown | 3 | 30% |