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Dietary flavonoid myricetin inhibits invasion and migration of radioresistant lung cancer cells (A549-IR) by suppressing MMP-2 and MMP-9 expressions through inhibition of the FAK-ERK signaling pathway.
Food Science & Nutrition ( IF 3.9 ) Pub Date : 2020-03-09 , DOI: 10.1002/fsn3.1495
Hye R Kang 1 , Jeong Y Moon 2 , Meran K Ediriweera 2 , Yeon W Song 3 , Moonjae Cho 1, 4 , Dharanibalan Kasiviswanathan 4 , Somi K Cho 1, 2, 3, 5
Affiliation  

Myricetin is a commonly found dietary flavonoid. In the present study, we investigated the effects of myricetin on migration and invasion of radioresistant lung cancer cells (A549‐IR). Transcriptome analysis of A549‐IR cells identified several differentially expressed genes (DEGs) in A549‐IR cells compared to parental A549 cells. Functional enrichment analysis revealed that most of the DEGs were linked with PI3K‐AKT signaling, proteoglycans, focal adhesion, and ECM–receptor interactions. A549‐IR cells demonstrated enhanced migratory potential with increased expression of vimentin, snail and slug, and reduced expression of E‐cadherin. A549‐IR cells exposed to myricetin displayed reduced migration and suppressed MMP‐2 and MMP‐9 expression. Notably, myricetin inhibited the phosphorylation of focal adhesion kinase (FAK) and altered the F‐actin/G‐actin ratio in A549‐IR cells, without modulation of EMT markers. These findings suggest that myricetin can inhibit migration of A549‐IR cells by suppressing MMP‐2 and MMP‐9 expressions through inhibition of the FAK‐ERK signaling pathway.

中文翻译:

膳食类黄酮杨梅素通过抑制FAK-ERK信号通路抑制MMP-2和MMP-9的表达,从而抑制了抗辐射肺癌细胞(A549-IR)的侵袭和迁移。

杨梅素是一种常见的饮食类黄酮。在本研究中,我们研究了杨梅素对放射性抗性肺癌细胞(A549-IR)迁移和侵袭的影响。与亲本A549细胞相比,A549-IR细胞的转录组分析确定了A549-IR细胞中的几个差异表达基因(DEG)。功能富集分析表明,大多数DEG与PI3K-AKT信号传导,蛋白聚糖,粘着斑和ECM-受体相互作用有关。A549-IR细胞表现出增强的迁移潜能,波形蛋白,蜗牛和and的表达增加,而E-钙黏着蛋白的表达减少。暴露于杨梅素的A549-IR细胞显示出减少的迁移并抑制了MMP-2和MMP-9的表达。值得注意的是 杨梅素抑制A549-IR细胞中的粘着斑激酶(FAK)的磷酸化并改变F-actin / G-actin比例,而无需调节EMT标记。这些发现表明,杨梅素可以通过抑制FAK-ERK信号通路来抑制MMP-2和MMP-9的表达,从而抑制A549-IR细胞的迁移。
更新日期:2020-03-09
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