已发表论文

氧化苦参碱通过抑制 αβ3 整合素/FAK/PI3K/Akt 信号激活来逆转乳腺癌细胞的上皮 - 间质转化

 

Authors Chen Y, Chen L, Zhang JY, Chen ZY, Liu T, Zhang YY, Fu LY, Fan SQ, Zhang MQ, Gan S, Zhang N, Shen XC

Received 17 March 2019

Accepted for publication 17 July 2019

Published 8 August 2019 Volume 2019:12 Pages 6253—6265

DOI https://doi.org/10.2147/OTT.S209056

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Ms Shreya Arora

Peer reviewer comments 2

Editor who approved publication: Dr XuYu Yang

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 and methods: 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 αβ3 integrin/focal adhesion kinase (FAK)/phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling transduction. Fibronectin, a physiologic ligand of αβ3 integrin, was used to stimulate αβ3 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 α and β3 integrin and their co-localization. It also inhibited αβ3 integrin downstream activation by suppressing the phosphorylation of FAK, PI3K, and Akt. Furthermore, oxymatrine prevented fibronectin-induced EMT and αβ3 integrin/FAK/PI3K/Akt signaling activation.
Conclusion: Our results revealed that oxymatrine effectively reversed EMT in breast cancer cells by depressing αβ3 integrin/FAK/PI3K/Akt signaling. Thus, oxymatrine could be a potential therapeutic candidate with anti-metastatic potential for the treatment of breast cancer.
Keywords: oxymatrine, breast cancer, αβ3 integrin, epithelial-mesenchymal transition




Figure 5 The effects of oxymatrine on FN-induced...