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Luteolin exerts pro-apoptotic effect and anti-migration effects on A549 lung adenocarcinoma cells through the activation of MEK/ERK signaling pathway

机译:木犀草素通过激活MEK / ERK信号通路对A549肺腺癌细胞发挥促凋亡和抗迁移作用

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An increasing amount of evidence suggests that luteolin, a common dietary flavonoid that is widely distributed in plants and foods, has been shown to be protective against cancer. However, the precise underlying mechanisms of its action against lung cancer are still poorly understood. In the present study, we investigated whether luteolin exhibits the anti-cancer effect in lung cancer through the induction of cell apoptosis and inhibition of cell migration, and whether mitogen-activated protein kinases (MAPKs) and Akt signaling pathways are required. Results revealed that luteolin exerted an anti-proliferation effect in a dose- and time-dependent manner in A549 lung adenocarcinoma cells, and induced apoptosis with a concomitant increase in the activation of caspases-3 and -9, diminution of Bcl-2, elevation in Bax expression, and the phosphorylation of MEK and its down-stream kinase ERK, as well as the activation of Akt. Luteolin also dramatically inhibited cell motility and migration in A549 cells. The inhibitor of MEK-ERK pathway protected against luteolin-induced cell death and suppressed the apoptosis-inducing and anti-migratory effects of luteolin, suggesting MEK-ERK signaling pathway plays an important role in mediating the pro-apoptotic effect and anti-migration effects of luteolin. Taken together, this study provides a new insight into the mode of action of luteolin on lung cancer. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
机译:越来越多的证据表明,木犀草素是一种常见的饮食类黄酮,广泛分布在植物和食品中,已显示出对癌症的保护作用。但是,其针对肺癌的确切作用机制仍知之甚少。在本研究中,我们调查了木犀草素是否通过诱导细胞凋亡和抑制细胞迁移而在肺癌中表现出抗癌作用,以及是否需要有丝分裂原激活的蛋白激酶(MAPK)和Akt信号通路。结果显示,木犀草素在A549肺腺癌细胞中具有剂量依赖性和时间依赖性的抗增殖作用,并诱导凋亡,并伴随着caspases-3和-9的激活,Bcl-2的减少,升高的升高。 Bax的表达,MEK及其下游激酶ERK的磷酸化以及Akt的激活。木犀草素还显着抑制A549细胞的细胞运动和迁移。 MEK-ERK通路的抑制剂可防止木犀草素诱导的细胞死亡,并抑制木犀草素的凋亡诱导和抗迁移作用,这表明MEK-ERK信号通路在介导促凋亡作用和抗迁移作用中起重要作用。木犀草素。总之,这项研究为木犀草素对肺癌的作用方式提供了新的见解。 (C)2016 Elsevier Ireland Ltd.保留所有权利。

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