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白杨素通过干扰 FOXM1/β-连环蛋白信号通路抑制黑色素瘤肿瘤转移。

Chrysin Inhibits Melanoma Tumor Metastasis via Interfering with the FOXM1/β-Catenin Signaling.

机构信息

College of Animal Sciences, Zhejiang University, Hangzhou 310058, China.

Radiation Oncology Department, University of California, San Francisco, California 94158, United States.

出版信息

J Agric Food Chem. 2020 Sep 2;68(35):9358-9367. doi: 10.1021/acs.jafc.0c03123. Epub 2020 Aug 24.

Abstract

Melanoma, which features high metastasis and high lethality, is one of the toughest tumors to treat. Chrysin, which is rich in various plants, has shown a great inhibitory effect on melanoma proliferation. Here, we evaluated the metastasis suppressive effect of chrysin on melanoma and . , chrysin effectively inhibited ankios resistance from 5 μM cell migration, invasion from 10 μM, and tube formation capacity of melanoma cells from 20 μM. We discovered that chrysin interfered with the mesenchymal-epithelial transition via regulating FOXM1/β-catenin signaling, as the expression of key regulatory factors was downregulated by chrysin treatment, and overexpression of FOXM1 will attenuate the antimetastasis effect of chrysin. We also tested chrysin on lung colonization in melanoma metastasis, where we found fewer tumors were formed in the lungs of chrysin-treated mice. In addition, the expression of FOXM1 was also downregulated by chrysin . Collectively, our findings suggested the ability of chrysin treatment to lower the metastatic rate of melanoma through regulating FOXM1/β-catenin signaling, indicating the application potential of chrysin for melanoma therapy.

摘要

黑色素瘤具有高转移和高致死率的特点,是最难治疗的肿瘤之一。富含于各种植物中的白杨素对黑色素瘤增殖表现出了很强的抑制作用。在这里,我们评估了白杨素对黑色素瘤转移的抑制作用。结果表明,白杨素有效抑制了黑色素瘤细胞在 5 μM 时的迁移、在 10 μM 时的侵袭和在 20 μM 时的管腔形成能力。我们发现白杨素通过调节 FOXM1/β-catenin 信号通路干扰上皮间质转化,因为白杨素处理会下调关键调节因子的表达,而过表达 FOXM1 会减弱白杨素的抗转移作用。我们还在黑色素瘤转移的肺定植中测试了白杨素,结果发现白杨素处理组小鼠肺部形成的肿瘤较少。此外,白杨素还下调了 FOXM1 的表达。总的来说,我们的研究结果表明,白杨素治疗通过调节 FOXM1/β-catenin 信号通路降低黑色素瘤的转移率,表明白杨素在黑色素瘤治疗中的应用潜力。

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