期刊
CANCER LETTERS
卷 314, 期 2, 页码 213-222出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2011.09.031
关键词
IFN-gamma; Autophagy; Cell growth; Cell death; HCC
类别
资金
- National Institute of Health [AI081678, DK62313, GM52021]
- National Natural Science Foundation of China [81001066]
Interferon-gamma (IFN-gamma) is a pleiotropic cytokine with immunomodulatory, anti-viral, and anti-proliferative effects. In this study, we examined the effects of IFN-gamma on autophagy and cell growth in human hepatocellular carcinoma (HCC) cells. IFN-gamma inhibited cell growth of Huh7 cells with non-apoptotic cell death. IFN-gamma induced autophagosome formation and conversion/turnover of microtubule associated protein 1 light chain 3 (LC3) protein. Furthermore, overexpression of IRF-1 also induced autophagy in Huh7 cells. Silencing IRF-1 expression with target small hairpin RNA blocked autophagy induced by IFN-gamma. Silencing of the autophagy signals Beclin-1 or Atg5 attenuated the inhibitory effect of IFN-gamma on Huh7 cells with decreased cell death. Additionally, IFN-gamma activated autophagy in freshly cultured human HCC cells. Together, these findings show that IFN-gamma induces autophagy through IRF-1 signaling pathway and the induction of autophagy contributes to the growth-inhibitory effect of IFN-gamma with cell death in human liver cancer cells. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
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