Oxymatrine reverses epithelial-mesenchymal transition in breast cancer cells by depressing αâ
¤ß3 integrin/FAK/PI3K/Akt signaling activation.
Onco Targets Ther
; 12: 6253-6265, 2019.
Article
em En
| MEDLINE
| ID: mdl-31496729
ABSTRACT
PURPOSE:
Oxymatrine, an alkaloid extracted from the Chinese herb Sophora flavescens Aiton, possesses anti-inflammatory, anti-immune, anti-hepatic fibrosis, and anti-cancer properties. However, the effects of oxymatrine on epithelial-mesenchymal transition (EMT) of breast cancer cells are still unclear.AIM:
The present study was performed to investigate whether oxymatrine reverses EMT in breast cancer cells and to explore the underlying molecular mechanisms. MATERIALS ANDMETHODS:
MTT assay was performed to evaluate cell viability. Wound-healing assay and transwell chamber assay were used to assess cell migration and invasion, respectively. Immunofluorescence and Western blot were used to study the expression of EMT-related molecules and αâ ¤ß3 integrin/focal adhesion kinase (FAK)/phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling transduction. Fibronectin, a physiologic ligand of αâ ¤ß3 integrin, was used to stimulate αâ ¤ß3 integrin signaling.RESULTS:
Our results demonstrated that oxymatrine effectively suppressed the viability of MDA-MB-231 and 4T1 breast cancer cells, and oxymatrine showed less cytotoxicity on normal breast mammary epithelial MCF-10A cells. In addition, oxymatrine reversed EMT in the MDA-MB-231 and 4T1 cells at nontoxic concentrations. Oxymatrine significantly inhibited cell migration and invasion, downregulated the expression of N-cadherin, vimentin, and Snail in MDA-MB-231 and 4T1 cells, but upregulated the expression of E-cadherin in 4T1 cells. The mechanism revealed that oxymatrine decreased the expression of αâ ¤ and ß3 integrin and their co-localization. It also inhibited αâ ¤ß3 integrin downstream activation by suppressing the phosphorylation of FAK, PI3K, and Akt. Furthermore, oxymatrine prevented fibronectin-induced EMT and αâ ¤ß3 integrin/FAK/PI3K/Akt signaling activation.CONCLUSION:
Our results revealed that oxymatrine effectively reversed EMT in breast cancer cells by depressing αâ ¤ß3 integrin/FAK/PI3K/Akt signaling. Thus, oxymatrine could be a potential therapeutic candidate with anti-metastatic potential for the treatment of breast cancer.
Texto completo:
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Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
Onco Targets Ther
Ano de publicação:
2019
Tipo de documento:
Article