Department of Clinical Pharmacy, College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210029, PR China.
Mol Med Rep. 2012 Jul;6(1):232-8. doi: 10.3892/mmr.2012.884. Epub 2012 Apr 23.
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.
缺氧诱导的上皮间质转化（EMT）是癌症转移的一个重要步骤。木樨草素是一种广泛存在于植物中的类黄酮，是一种新型的抗癌药物。然而，其抗癌作用的机制尚不清楚。在这项研究中，我们首次证明，木樨草素抑制培养的人非小细胞肺癌细胞中缺氧诱导的 EMT，这表现在缺氧诱导的 EMT 降低了 E-钙粘蛋白和其他上皮标志物的表达，增加了 N-钙粘蛋白、波形蛋白和其他间充质标志物的表达；木樨草素显著减弱了这些作用。此外，木樨草素还抑制了细胞的缺氧诱导增殖、迁移和黏附。此外，我们揭示木樨草素抑制整合素β1 和粘着斑激酶（FAK）的表达。由于整合素β1 和 FAK 信号与 EMT 的形成密切相关，这些结果表明，木樨草素通过抑制整合素β1 和 FAK 的表达来抑制缺氧诱导的 EMT，至少部分如此。
