期刊
CANCER BIOLOGY & THERAPY
卷 13, 期 6, 页码 435-442出版社
TAYLOR & FRANCIS INC
DOI: 10.4161/cbt.19295
关键词
ATF4; hepatoma; apoptosis; glutathione; chemoresistance
类别
资金
- Tianjin Municipal Science and Technology Commission [08ZCGYSH04700]
- National Science and Technology Infrastructure Program [2009BAI86B05]
- National Development Plan of High Technology 863 [2007AA021010]
- National Development Plan of High Technology 973 [2007CB914804]
It has been reported that activating transcription factor 4 (ATF4) increases the processes of tumor growth, metastasis and drug resistance. However, the role played by ATF4 in chemoresistance of hepatocellular carcinoma (HCC) remains unknown. Clarification of this role of ATF4 in HCC could greatly benefit the efficacy of clinical treatment of HCC. In this study, we found that ATF4 was overexpressed in about 50.7% of HCC tissues. In fact knockdown of ATF4 significantly increased the cytotoxicity of cisplatin in both in vitro and in vivo assays, while overexpression of this molecule dramatically decreased the sensitivity of HCC cell lines to cisplatin. Additionally, we found that synthesis of glutathione was significantly reduced in HCC cell lines subjected to ATF4 knockdown. Taken together, these results demonstrate that ATF4 can increase resistance to cisplatin in HCC by increased biosynthesis of glutathione, and that this may be a potent novel target for the future development of anti-HCC drugs.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据