Sevoflurane inhibits invasion and migration of lung cancer cells by inactivating the p38 MAPK signaling pathway

Abstract

Sevoflurane is used widely during lung cancer surgery. However, the effect of sevoflurane on the invasion and migration of lung carcinoma cells remains unclear. The aims of this study were to explore the role of matrix metalloproteinase (MMP)-2 and MMP-9 in the effect of sevofluane on the invasion and the role of fascin and ezrin on the effect of sevofluane on the migration of human lung adenocarcinoma A549 cells. We also investigated whether sevoflurane regulates the expression of these molecules through the p38 mitogen-activated protein kinase (MAPK) signaling pathway. The invasion of cells was evaluated using the Transwell invasion assay, and the migration of cells was determined using the wound healing assay. The expression of MMP-2, MMP-9, ezrin, fascin, and phospho-p38 MAPK in cells was determined by western blotting. A significant inhibition of cell invasion and migration was found in A549 cells which had been treated with sevoflurane. The data also revealed that sevoflurane could decrease the phosphorylation level of p38 MAPK, which is involved in the downregulation of MMP-2, MMP-9, fascin, and ezrin expression, accompanied by a concomitant inhibition of the invasion and migration of A549 cells. SB203580, a p38 MAPK inhibitor, augmented the downregulation of the expression of these proteins. The anti-invasion effect of sevoflurane on A549 cells was associated with a downregulation of both MMP-2 and MMP-9 expression, while the anti-migration effect was associated with a downregulation of both fascin and ezrin expression. These effects could occur partly as a result of inactivation of the p38 MAPK signaling pathway.