Resveratrol Inhibits the Migration and Metastasis of MDA-MB-231 Human Breast Cancer by Reversing TGF-β1-Induced Epithelial-Mesenchymal Transition.

Yang Sun,Shi-Bing Su,Yi-Yu Lu,Ming Zhao,Qi-Long Chen,Hui Zhang,Qian-Mei Zhou

doi:10.3390/molecules24061131

Abstract

Metastasis is a major cause of death in patients with breast cancer. In the process of cancer development, epithelial-mesenchymal transition (EMT) is crucial to promoting the invasion and migration of tumor cells. In a previous study, the role of resveratrol in migration and metastasis was investigated in MDA-MB-231 (MDA231) human breast cancer cells and a xenograft-bearing mouse model. Additionally, the related mechanism was explored. In the present study, in vitro Transwell assays showed that resveratrol can inhibit the migration of transforming growth factor (TGF)-β1-induced MDA231 cells in a concentration-dependent manner. An enzyme-linked immunosorbent assay (ELISA) showed that resveratrol can reduce the secretion of matrix metalloproteinase (MMP)-2 and MMP-9. Immunofluorescence was performed to confirm the expression of EMT-related markers. Immunofluorescence assays confirmed that resveratrol changed the expression of the EMT-related markers E-cadherin and vimentin. Western blot analysis demonstrated that resveratrol decreased the expression levels of MMP-2, MMP-9, Fibronectin, α-SMA, P-PI3K, P-AKT, Smad2, Smad3, P-Smad2, P-Smad3, vimentin, Snail1, and Slug, as well as increased the expression levels of E-cadherin in MDA231 cells. In vivo, resveratrol inhibited lung metastasis in a mouse model bearing MDA231 human breast cancer xenografts without marked changes in body weight or liver and kidney function. These results indicate that resveratrol inhibits the migration of MDA231 cells by reversing TGF-β1-induced EMT and inhibits the lung metastasis of MDA231 human breast cancer in a xenograft-bearing mouse model.

Highlights

One of the most common cancers in women is breast cancer, which seriously impairs the patient’s physical and mental health
BT549 (BT-549) cells were treated with different concentrations of resveratrol for three days to determine the effect of resveratrol on breast cancer cell survival
Our results showed that the expression levels of Smad3, P-Smad3, Slug, and Snail1 were decreased by resveratrol (Figures 3C and 5A), which may be related to the role of resveratrol in reversing transforming growth factor (TGF)-β1-induced epithelial-mesenchymal transition (EMT)

Summary

Introduction

One of the most common cancers in women is breast cancer, which seriously impairs the patient’s physical and mental health. Epithelial-mesenchymal transition (EMT) is a process where under some specific physiological or pathological conditions, epithelial cells lose their polarity and become mesenchymal cells with the ability to move freely and actively in the cell matrix [3]. EMT is characterized by the loss of epithelial cell polarity and the acquisition of stromal features, including (1) decreased expression of cell adhesion molecules, which leads to intercellular junction disruption and cell movement and (2) transformation of the keratin cytoskeleton into a waveform protein cytoskeleton. Studies have found that in all types of cells, the EMT phenomenon is closely associated with tumor invasion and metastasis and is quite important in the invasion and metastasis of ovarian cancer, breast cancer, colon cancer, lung cancer, prostate cancer, oral cancer, liver cancer, and various other types of cancer [5]

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