Oxymatrine reverses epithelial-mesenchymal transition in breast cancer cells by depressing [[alpha].sub.V][[beta].sub.3] integrin/FAK/PI3K/Akt signaling activation

• Published in: OncoTargets and therapy 2019-08, p.6253
• Main Authors: Chen, Yan, Chen, Lin, Zhang, Jing-Yu, Chen, Zong-Yue, Liu, Ting-Ting, Zhang, Yan-Yan, Fu, Ling-Yun, Fan, Shuang-Qin, Zhang, Min-Qin, Gan, Shi-Quan, Zhang, Nen-Ling, Shen, Xiang-Chun
• Format: Article
• Language: English
• Subjects: Alkaloids; Anti-inflammatory agents; Breast cancer; Cancer cells; Cancer metastasis; Cancer research; Cancer treatment; Cellular signal transduction; Fibronectins; Fibrosis; Fluorescent antibody technique; Integrins; Protein kinases; Stem cells
• ISSN: 1178-6930; 1178-6930
• DOI: 10.2147/OTT.S209056

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 [[alpha].sub.V][[beta].sub.3] integrin/focal adhesion kinase (FAK)/phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling transduction. Fibronectin, a physiologic ligand of [[alpha].sub.V][[beta].sub.3] integrin, was used to stimulate [[alpha].sub.V][[beta].sub.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 [[alpha].sub.V] and [[beta].sub.3] integrin and their co-localization. It also inhibited [[alpha].sub.V][[beta].sub.3] integrin downstream activation by suppressing the phosphorylation of FAK, PI3K, and Akt. Furthermore, oxymatrine prevented fibronectin-induced EMT and [[alpha].sub.V][[beta].sub.3] integrin/FAK/PI3K/Akt signaling activation. Conclusion: Our results revealed that oxymatrine effectively reversed EMT in breast cancer cells by depressing [[alpha].sub.V][[beta].sub.3] 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, [[alpha].sub.V][[beta].sub.3] integrin, epithelial-mesenchymal transition