Research Center for Traditional Chinese Medicine Complexity System, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
AntiCancer Inc., San Diego, CA 92100, USA.
Molecules. 2019 Mar 21;24(6):1131. doi: 10.3390/molecules24061131.
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.
转移是乳腺癌患者死亡的主要原因。在癌症发展过程中，上皮-间充质转化（EMT）对于促进肿瘤细胞的侵袭和迁移至关重要。在之前的一项研究中，研究了白藜芦醇在 MDA-MB-231（MDA231）人乳腺癌细胞和异种移植荷瘤小鼠模型中的迁移和转移作用，并探讨了相关机制。在本研究中，体外 Transwell 实验表明，白藜芦醇可以浓度依赖性地抑制转化生长因子（TGF）-β1 诱导的 MDA231 细胞的迁移。酶联免疫吸附试验（ELISA）表明，白藜芦醇可以减少基质金属蛋白酶（MMP）-2 和 MMP-9 的分泌。免疫荧光实验用于确认 EMT 相关标志物的表达。免疫荧光实验证实，白藜芦醇改变了 EMT 相关标志物 E-钙粘蛋白和波形蛋白的表达。Western blot 分析表明，白藜芦醇降低了 MMP-2、MMP-9、纤维连接蛋白、α-SMA、P-PI3K、P-AKT、Smad2、Smad3、P-Smad2、P-Smad3、波形蛋白、Snail1 和 Slug 的表达水平，并增加了 MDA231 细胞中 E-钙粘蛋白的表达水平。在体内，白藜芦醇抑制了 MDA231 人乳腺癌异种移植荷瘤小鼠模型中的肺转移，而体重或肝肾功能无明显变化。这些结果表明，白藜芦醇通过逆转 TGF-β1 诱导的 EMT 抑制 MDA231 细胞的迁移，并抑制异种移植荷瘤小鼠模型中 MDA231 人乳腺癌的肺转移。
