Department of Anesthesiology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
J Anesth. 2012 Jun;26(3):381-92. doi: 10.1007/s00540-011-1317-y. Epub 2012 Feb 17.
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.
七氟醚在肺癌手术中广泛应用。然而，七氟醚对肺癌细胞侵袭和迁移的影响尚不清楚。本研究旨在探讨基质金属蛋白酶（MMP）-2 和 MMP-9 在七氟醚对人肺腺癌 A549 细胞侵袭作用中的作用，以及 fascin 和 ezrin 在七氟醚对人肺腺癌 A549 细胞迁移作用中的作用。我们还研究了七氟醚是否通过丝裂原活化蛋白激酶（MAPK）p38 信号通路调节这些分子的表达。
采用 Transwell 侵袭实验评估细胞侵袭，采用划痕愈合实验检测细胞迁移。Western blot 检测 MMP-2、MMP-9、ezrin、fascin 和磷酸化 p38 MAPK 的表达。
七氟醚处理 A549 细胞后，细胞侵袭和迁移明显受到抑制。结果还表明，七氟醚可降低参与 MMP-2、MMP-9、fascin 和 ezrin 表达下调的 p38 MAPK 的磷酸化水平，伴随 A549 细胞侵袭和迁移的抑制。p38 MAPK 抑制剂 SB203580 增强了这些蛋白表达的下调。
七氟醚对 A549 细胞的抗侵袭作用与 MMP-2 和 MMP-9 表达下调有关，而抗迁移作用与 fascin 和 ezrin 表达下调有关。这些作用可能部分是由于 p38 MAPK 信号通路失活所致。
