Digoxin inhibits migration and invasion of human gastric carcinoma MKN45 cells through down-regulation of AEG-1 / 生理学报

ABSTRACT

This study was designed to investigate the effect of digoxin on migration and invasion of human gastric carcinoma MKN45 cells and its possible mechanism. MKN45 cells were treated with different concentrations of digoxin for 24 h. The shRNA-AEG-1 plasmid was transfected into MKN45 cells via lipofectamine to block the expression of astrocyte elevated gene-1 (AEG-1). Western blot was used to analyze the protein levels of matrix metalloproteinase-9 (MMP-9), E-cadherin and AEG-1. The result showed that digoxin reduced the abilities of migration and invasion (P < 0.05), up-regulated the protein level of E-cadherin (P < 0.05), and down-regulated the protein levels of MMP-9 and AEG-1 (P < 0.05) in MKN45 cells in a dose-dependent manner. Compared with shControl group, shAGE-1 group showed inhibited cellular migration and invasion, higher expression level of E-cadherin, and lower expression levels of MMP-9 and AEG-1. These results suggest that digoxin suppresses the migration and invasion of human gastric carcinoma MKN45 cells in a dose-dependent manner through inhibiting the expression of AEG-1, and then resulting in the up-regulation of the protein expression of E-cadherin and the down-regulation of the protein expression of MMP-9.