Disulfiram combined with copper inhibits metastasis and epithelial-mesenchymal transition in hepatocellular carcinoma through the NF-κB and TGF-ß pathways.
J Cell Mol Med
; 22(1): 439-451, 2018 01.
Article
en En
| MEDLINE
| ID: mdl-29148232
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-ß 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-ß signalling. Our study indicates the potential of DSF/Cu for therapeutic use.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
FN-kappa B
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Factor de Crecimiento Transformador beta
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Carcinoma Hepatocelular
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Cobre
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Disulfiram
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Transición Epitelial-Mesenquimal
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Neoplasias Hepáticas
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Neoplasias Pulmonares
Tipo de estudio:
Prognostic_studies
Límite:
Animals
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Humans
Idioma:
En
Año:
2018
Tipo del documento:
Article