Oroxylin A inhibits hypoxia-induced invasion and migration of MCF-7 cells by suppressing the Notch pathway

Oroxylin A inhibits hypoxia-induced invasion and migration of MCF-7 cells by suppressing the Notch pathway
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Oroxylin A 通过抑制 Notch 通路抑制缺氧诱导的 MCF-7 细胞侵袭和迁移

DOI:
10.1097/cad.0000000000000103
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发表时间:
2014-08-01
期刊:
影响因子:
2.3
通讯作者:
Lu, Na
Lu, Na
中科院分区:
医学4区
文献类型:
--
作者:
Cheng, Yao;Zhao, Kai;Lu, Na

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肿瘤的侵袭和转移阻碍了癌症的治疗和预后。在本研究中,我们研究了从黄芩中提取的天然化合物Oroxylin A对三种不同的肿瘤细胞系Mcf-7、DU145和HepG2的侵袭和迁移的抑制作用。结果提示,Oroxylin A可抑制缺氧诱导的上述三种细胞的迁移和侵袭。为了研究其作用机制,在MCF-7细胞上进行了研究,发现Oroxylin A可以调节MCF-7细胞中E-钙粘蛋白、N-钙粘蛋白和Vimentin等相关标志物的表达。研究还发现,Oroxylin A通过抑制Notch途径抑制低氧诱导的MCF-7细胞的侵袭和迁移。Oroxylin A可抑制N1ICD移位到细胞核并与上皮-间充质转化相关转录因子Snail结合,从而抑制MCF-7细胞的侵袭和迁移。因此,通过抑制低氧诱导的Notch通路,Oroxylin A有望成为抗肿瘤转移治疗的候选药物。
Tumor invasion and migration obstructs the treatment and prognosis of cancer. In this research, we investigated the effect of oroxylin A, a natural compound extracted from Scutellaria radix, the root of Scutellaria baicalensis, on inhibition of the invasion and migration of three different tumor cell lines: MCF-7, DU145, and HepG2. The results suggested that oroxylin A could inhibit hypoxia-induced migration and invasion of the three cell lines mentioned above. To study the detailed mechanisms, studies were carried out on MCF-7 cells and it was found that oroxylin A could regulate the expression of related markers in MCF-7 cells including E-cadherin, N-cadherin, and Vimentin. It was also found that oroxylin A inhibited the hypoxia-induced invasion and migration of MCF-7 cells by suppressing the Notch pathway. Oroxylin A inhibited N1ICD translocating to the nucleus and binding to epithelial–mesenchymal transition-related transcription factor Snail, thus suppressing the invasion and migration of MCF-7 cells. Therefore, oroxylin A is expected to be a promising candidate for antimetastasis treatment through suppression of the hypoxia-induced Notch pathway.