Etomidate Suppresses Invasion and Migration of Human A549 Lung Adenocarcinoma Cells

Etomidate Suppresses Invasion and Migration of Human A549 Lung Adenocarcinoma Cells
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DOI:
10.21873/anticanres.13100
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发表时间:
2019-01-01
影响因子:
2
通讯作者:
Chung, Jing-Gung
Chung, Jing-Gung
中科院分区:
医学4区
文献类型:
--
作者:
Chu, Chin-Nan;Wu, King-Chuen;Chung, Jing-Gung

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背景/目的:静脉麻醉药依托咪酯已被证明具有抗癌作用,包括诱导细胞周期阻滞和细胞凋亡。然而,据我们所知,尚无依托咪酯对A549人肺腺癌细胞抗转移作用的报道。材料与方法:采用细胞活力、细胞黏附、明胶酶谱法、transwell迁移侵袭法和western blotting法观察依托咪酯对A549细胞的影响。结果:依托咪酯对A549细胞具有低细胞毒性,抑制细胞粘附,抑制细胞迁移和侵袭。依托咪酯处理48 h后,基质金属肽酶2 (MMP2)活性降低。western blotting分析结果显示,依托咪酯在A549细胞中作用24和48 h后,下调蛋白激酶C、MMP7、MMP1、MMP9和p-p-38的表达,上调RAS、磷酸肌肽3激酶和磷酸化细胞外信号相关激酶的表达。结论:依托咪酯通过抑制MMP1、MMP2、MMP7和MMP9的表达抑制肺腺癌A549细胞的迁移和侵袭,为肺癌治疗提供了潜在的治疗靶点。
Background/Aim: Etomidate, an intravenous anesthetic, has been shown to have anticancer effects, including induction of cell-cycle arrest and apoptosis. However, to our knowledge, there are no reports about the anti-metastasis effects of etomidate on A549 human lung adenocarcinoma cells. Materials and Methods: The cell viability, cell adhesion, gelatin zymography assay, transwell migration and invasion assay, and western blotting analysis were used to investigate the effects of etomidate on A549 cells. Results: In our study, etomidate showed low cytotoxicity, inhibited cell adhesion, and suppressed the migration and invasion in A549 cells. The activity of matrix metallopeptidase 2 (MMP2) was reduced by 48 h treatment of etomidate. Results of western blotting analysis indicated that etomidate down-regulated the expression of protein kinase C, MMP7, MMP1, MMP9, and p-p-38, but up-regulated that of RAS, phosphoinositide 3-kinase, and phosphor-extracellular-signal related kinase after 24 and 48 h treatment, in A549 cells. Conclusion: Etomidate suppressed the migration and invasion of lung adenocarcinoma A549 cells via inhibiting the expression of MMP1, MMP2, MMP7 and MMP9, and provides potential therapeutic targets for lung cancer treatment.