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

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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5742719/
https://www.ncbi.nlm.nih.gov/pubmed/29148232
http://dx.doi.org/10.1111/jcmm.13334
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author 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
author_facet 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
author_sort Li, Yi
collection PubMed
description 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.
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spelling pubmed-57427192018-01-04 Disulfiram combined with copper inhibits metastasis and epithelial–mesenchymal transition in hepatocellular carcinoma through the NF‐κB and TGF‐β pathways 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 J Cell Mol Med Original Articles 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. John Wiley and Sons Inc. 2017-11-17 2018-01 /pmc/articles/PMC5742719/ /pubmed/29148232 http://dx.doi.org/10.1111/jcmm.13334 Text en © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
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
Disulfiram combined with copper inhibits metastasis and epithelial–mesenchymal transition in hepatocellular carcinoma through the NF‐κB and TGF‐β pathways
title Disulfiram combined with copper inhibits metastasis and epithelial–mesenchymal transition in hepatocellular carcinoma through the NF‐κB and TGF‐β pathways
title_full Disulfiram combined with copper inhibits metastasis and epithelial–mesenchymal transition in hepatocellular carcinoma through the NF‐κB and TGF‐β pathways
title_fullStr Disulfiram combined with copper inhibits metastasis and epithelial–mesenchymal transition in hepatocellular carcinoma through the NF‐κB and TGF‐β pathways
title_full_unstemmed Disulfiram combined with copper inhibits metastasis and epithelial–mesenchymal transition in hepatocellular carcinoma through the NF‐κB and TGF‐β pathways
title_short Disulfiram combined with copper inhibits metastasis and epithelial–mesenchymal transition in hepatocellular carcinoma through the NF‐κB and TGF‐β pathways
title_sort disulfiram combined with copper inhibits metastasis and epithelial–mesenchymal transition in hepatocellular carcinoma through the nf‐κb and tgf‐β pathways
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5742719/
https://www.ncbi.nlm.nih.gov/pubmed/29148232
http://dx.doi.org/10.1111/jcmm.13334
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