Disulfiram combined with copper inhibits metastasis and epithelial-mesenchymal transition in hepatocellular carcinoma through the NF-κB and TGF-β pathways

作者：Li, Yi; Wang, Li-Hui; Zhang, Hao-Tian; Wang, Ya-Ting; Liu, Shuai; Zhou, Wen-Long; Yuan, Xiang-Zhong; Li, Tian-Yang; Wu, Chun-Fu^*; Yang, Jing-Yu^*

来源：JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, 2018, 22(1): 439-451.

DOI：10.1111/jcmm.13334

• disulfiram
• copper
• metastasis
• EMT
• TGF-beta

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.

• 出版日期2018-1
• 单位沈阳药科大学