期刊
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
卷 22, 期 1, 页码 439-451出版社
WILEY
DOI: 10.1111/jcmm.13334
关键词
disulfiram; copper; metastasis; EMT; TGF-beta
资金
- National Key Scientific Project for New Drug Discovery and Development [2013ZX09301305]
- National High Technology Research and Development Program of China (863 Program) [2012AA020305]
- Program for Liaoning Innovative Research Team in University [LT2014023]
Late-stage hepatocellular carcinoma (HCC) usually has a low survival rate because of the high risk of metastases and the lack of an effective cure. Disulfiram (DSF) has copper (Cu)-dependent anticancer properties invitro and invivo. The present work aims to explore the anti-metastasis effects and molecular mechanisms of DSF/Cu on HCC cells both invitro and invivo. The results showed that DSF inhibited the proliferation, migration and invasion of HCC cells. Cu improved the anti-metastatic activity of DSF, while Cu alone had no effect. Furthermore, DSF/Cu inhibited both NF-kappa B and TGF-beta signalling, including the nuclear translocation of NF-kappa B subunits and the expression of Smad4, leading to down-regulation of Snail and Slug, which contributed to phenotype epithelial-mesenchymal transition (EMT). Finally, DSF/Cu inhibited the lung metastasis of Hep3B cells not only in a subcutaneous tumour model but also in an orthotopic liver metastasis assay. These results indicated that DSF/Cu suppressed the metastasis and EMT of hepatic carcinoma through NF-kappa B and TGF-beta signalling. Our study indicates the potential of DSF/Cu for therapeutic use.
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