Emodin inhibits epithelialmesenchymal transition and metastasis of triple negative breast cancer via antagonism of CCchemokine ligand 5 secreted from adipocytes.
Int J Mol Med
; 42(1): 579-588, 2018 Jul.
Article
em En
| MEDLINE
| ID: mdl-29693154
ABSTRACT
Triple negative breast cancer (TNBC) has the lowest survival rate of the breast cancer subtypes owing to its aggressive and metastatic behavior. It has been reported that peritumoral adipose tissue contributes to the cell invasiveness and dissemination of TNBC. Emodin is an active anthraquinone derivative isolated from Rheum palmatum, with anticancer properties that have been reported to inhibit lung metastasis in a nude mouse xenograft model. In the present study, the effects of emodin on human TNBC cells and adipocytes were investigated in vivo and in vitro. The TNBC cell lines MDAMB231 and MDAMB453 were cocultured with human adipocytes and treated with either emodin or epirubicin. Cell proliferation was assessed by MTT assay and migration and invasion were examined using a wound healing assay and a Transwell assay. interleukin8, CCchemokine ligand 5 (CCL5) and insulinlike growth factor1 levels in the culture supernatants were detected by ELISA. The epithelialmesenchymal transition (EMT) or metastasis associated markers were determined by western blot analysis. Nude mice fed with a high fat and sugar diet were used investigate the in vivo effect of emodin. The results showed that emodin inhibited TNBC proliferation and invasion more efficiently than epirubicin when cocultured with adipocytes by downregulating the level of CCL5 in adipocyte supernatants; inhibiting the expression level of protein kinase B (AKT); and activating glycogen synthase kinase3i (GSK3) and ßcatenin. This led to the suppressed expression of EMT and invasionassociated markers, including vimentin, snail, matrix metalloproteinase (MMP)2 and MMP9, and upregulation of Ecadherin, contributing to the inhibition of invasion. The in vivo assay showed that emodin inhibited tumor growth, and suppressed the lung and liver metastasis of TNBC cells by decreasing the secretion of CCL5 in mice fed a high fat and sugar diet more efficiently when compared with epirubicin. In conclusion, emodin inhibited the secretion of CCL5 from adipocytes, inhibited the EMT of TNBC cells, and inhibited tumor growth and lung and liver metastasis, which indicated a novel role of emodin in preventing the metastasis of TNBC.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Emodina
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Adipócitos
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Quimiocina CCL5
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Transição Epitelial-Mesenquimal
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Neoplasias de Mama Triplo Negativas
Tipo de estudo:
Prognostic_studies
Limite:
Adult
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Animals
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Female
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Humans
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Middle aged
Idioma:
En
Revista:
Int J Mol Med
Ano de publicação:
2018
Tipo de documento:
Article