Open AccessDisulfiram combined with copper inhibits metastasis and epithelial–mesenchymal transition in hepatocellular carcinoma through the NF ‐κB and TGF ‐β pathways
Author(s) -
Li Yi,
Wang LiHui,
Zhang HaoTian,
Wang YaTing,
Liu Shuai,
Zhou WenLong,
Yuan XiangZhong,
Li TianYang,
Wu ChunFu,
Yang JingYu
Publication year - 2018
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13334
Subject(s) - epithelial–mesenchymal transition , metastasis , slug , cancer research , hepatocellular carcinoma , in vivo , in vitro , chemistry , nf κb , medicine , cancer , apoptosis , biology , biochemistry , microbiology and biotechnology
Abstract 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 in vitro and in vivo . The present work aims to explore the anti‐metastasis effects and molecular mechanisms of DSF /Cu on HCC cells both in vitro and in vivo . 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 ‐κB and TGF ‐β signalling, including the nuclear translocation of NF ‐κB 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 ‐κB and TGF ‐β signalling. Our study indicates the potential of DSF /Cu for therapeutic use.