Inhibition of hypoxia-induced epithelial mesenchymal transition by luteolin in non-small cell lung cancer cells.
Inhibition of hypoxia-induced epithelial mesenchymal transition by luteolin in non-small cell lung cancer cells.
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DOI：
10.3892/mmr.2012.884
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发表时间：
2012-07
影响因子：
3.4
通讯作者：
Junshan Ruan;Lei Zhang;Ling-geng Yan;Yu-ping Liu;Zhi-qiang Yue;Li Chen;Aiyun Wang;Wenxing Chen;Shizhong Zheng;Shao-Ming Wang;Yin Lu
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文献类型：
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作者：
Junshan Ruan;Lei Zhang;Ling-geng Yan;Yu-ping Liu;Zhi-qiang Yue;Li Chen;Aiyun Wang;Wenxing Chen;Shizhong Zheng;Shao-Ming Wang;Yin Lu
缺氧诱导的上皮间质转化（EMT）是肿瘤转移的重要步骤。木犀草素是一种广泛存在于植物中的黄酮类化合物，是一种新型的抗癌药物。然而，其抗癌作用的机制仍不明确。在这项研究中，我们第一次证明，木犀草素抑制缺氧诱导的EMT在培养的人非小细胞肺癌细胞，这是证明了缺氧诱导的EMT的表达减少E-钙粘蛋白和其他上皮标记物，并增加N-钙粘蛋白，波形蛋白和其他间充质标记物的表达，这些影响显着减弱木犀草素。此外，毛地黄黄酮还能抑制缺氧诱导的细胞增殖、运动和粘附。此外，我们还发现毛地黄黄酮可抑制整合素β1和粘着斑激酶（FAK）的表达，整合素β1和FAK信号通路与EMT的形成密切相关，提示毛地黄黄酮至少部分通过抑制整合素β1和FAK的表达来抑制缺氧诱导的EMT。
Hypoxia-induced epithelial mesenchymal transition (EMT) is an essential step in cancer metastasis. Luteolin, a flavonoid that is widely distributed in plants, is a novel anticancer agent. However, the mechanism underlying its anticancer effects remains undefined. In this study, for the first time, we demonstrate that luteolin inhibits hypoxia-induced EMT in human non-small cell lung cancer cells in culture, which is demonstrated by the fact that hypoxia-induced EMT reduced the expression of E-cadherin and other epithelial markers and increased the expression of N-cadherin, vimentin and other mesenchymal markers; these effects were markedly attenuated by luteolin. In addition, luteolin also inhibited hypoxia-induced proliferation, motility and adhesion in the cells. Furthermore, we reveal that luteolin inhibits the expression of integrin β1 and focal adhesion kinase (FAK).Since integrin β1 and FAK signaling are closely related to EMT formation, these results suggest that luteolin inhibits hypoxia-induced EMT, at least in part, by inhibiting the expression of integrin β1 and FAK.