MgCl(2) and ZnCl(2) promote human umbilical vein endothelial cell migration and invasion and stimulate epithelial-mesenchymal transition via the Wnt/β-catenin pathway

Previous studies have demonstrated that magnesium and zinc ions promote the migration and epithelial-mesenchymal transition (EMT) of cancer/endothelial cells. However, the impact of MgCl(2) and ZnCl(2) on the migration, invasion and EMT of human umbilical vein endothelial cells (HUVECs) and the involved mechanisms remain unclear. In the present study, HUVECs were incubated with various doses of MgCl(2) and ZnCl(2). The optimum concentrations of MgCl(2) and ZnCl(2) were selected by MTT assay. The migration and invasion capabilities of HUVECs were analyzed by Transwell assays. Subsequently, the expression of matrix metalloproteinase (MMP)-2 and MMP-9 mRNA and protein were determined by reverse transcription-quantitative polymerase chain reaction, western blotting and ELISA. MMP-2 and MMP-9 activities were measured by gelatin zymography. Immunofluorescence staining was performed to investigate cytoskeletal dynamics using Acti-stain™ 488 Fluorescent Phalloidin. Subsequently, the expression of EMT-related markers at the mRNA and protein levels and the activation of Wnt/β-catenin signaling were analyzed. The results identified increases in MMP-2 and MMP-9 expression and activity, indicating that MgCl(2) and ZnCl(2) promoted HUVEC migration and invasion. In addition, MgCl(2) and ZnCl(2) treatment induced cytoskeleton remodeling and stimulated EMT via activation of the Wnt/β-catenin signaling pathway, characterized by a decrease in E-cadherin and increases in N-cadherin, vimentin and Snail. These results suggest that MgCl(2) and ZnCl(2) may enhance the migration and invasion capabilities of HUVECs and promote EMT through the Wnt/β-catenin pathway.