Oxymatrine reverses epithelial-mesenchymal transition in breast cancer cells by depressing αⅤβ3 integrin/FAK/PI3K/Akt signaling activation

Content Provider	Scilit
Author	Chen, Yan Chen, Lin Zhang, Jing-Yu Chen, Zong-Yue Ting-Ting, Liu Zhang, Yan-Yan Fu, Ling-Yun Fan, Shuang-Qin Zhang, Min-Qin Gan, Shi-Quan Zhang, Nen-Ling Shen, Xiang-Chun
Copyright Year	2019
Description	Journal: OncoTargets and therapy
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 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 $α_{Ⅴ}β_{3}$ integrin/focal adhesion kinase (FAK)/phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling transduction. Fibronectin, a physiologic ligand of $α_{Ⅴ}β_{3}$ integrin, was used to stimulate $α_{Ⅴ}β_{3}$ 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 $α_{Ⅴ}$ and $β_{3}$ integrin and their co-localization. It also inhibited $α_{Ⅴ}β_{3}$ integrin downstream activation by suppressing the phosphorylation of FAK, PI3K, and Akt. Furthermore, oxymatrine prevented fibronectin-induced EMT and $α_{Ⅴ}β_{3}$ integrin/FAK/PI3K/Akt signaling activation. Conclusion: Our results revealed that oxymatrine effectively reversed EMT in breast cancer cells by depressing $α_{Ⅴ}β_{3}$ integrin/FAK/PI3K/Akt signaling. Thus, oxymatrine could be a potential therapeutic candidate with anti-metastatic potential for the treatment of breast cancer.
Related Links	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6691185/pdf https://www.dovepress.com/getfile.php?fileID=51876
Ending Page	6265
Page Count	13
Starting Page	6253
ISSN	11786930
DOI	10.2147/ott.s209056
Journal	OncoTargets and therapy
Volume Number	ume 12
Language	English
Publisher	Informa UK Limited
Publisher Date	2019-08-01
Access Restriction	Open
Subject Keyword	Journal: OncoTargets and therapy Integrative and Complementary Medicine Breast Cancer Αⅴβ3 Integrin Epithelial-mesenchymal Transition
Content Type	Text
Subject	Pharmacology (medical) Oncology