Department of Medical Biotechnology and Laboratory Sciences, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan; Graduate Institute of Biomedical Sciences, Division of Biotechnology, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan; Center for Molecular and Clinical Immunology, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan.
Department of Medical Biotechnology and Laboratory Sciences, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan; Graduate Institute of Biomedical Sciences, Division of Biotechnology, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan.
J Ethnopharmacol. 2018 Jun 28;220:239-249. doi: 10.1016/j.jep.2018.03.041. Epub 2018 Mar 30.
The medicinal mushroom Antrodia cinnamomea has been used to treat cancer but its anti-angiogenic effects have not been studied in detail.
The main objective of this study was to determine the molecular mechanism of activity underlying the anti-angiogenic effects of A. cinnamomea.
The effects of an A. cinnamomea ethanol extract (ACEE) on cell migration and microvessel formation were investigated in endothelial cells in vitro and Matrigel plugs implanted into mice in vivo. Activation of intracellular signaling pathways was examined using Western blotting. Protein expression was assessed using immunohistochemistry in a mouse model of lung metastasis.
We show that treatment with ACEE inhibits cell migration and tube formation in human umbilical vein endothelial cells (HUVECs). ACEE suppresses phosphorylation of vascular endothelial growth factor receptor 2 (VEGFR2) and expression of pro-angiogenic kinases in vascular endothelial growth factor (VEGF)-treated HUVECs, in addition to reducing expression of Janus kinase 2 (JAK2) and phosphorylation of signal transducer and activator of transcription 3 (STAT3). ACEE treatment inhibits VEGF-induced microvessel formation in Matrigel plugs in vivo. In addition, ACEE significantly reduces VEGFR2 expression in Lewis lung carcinoma cells and downregulates the expression of cluster of differentiation 31 (CD31) and VEGFR2 in murine lung metastases.
These results indicate that A. cinnamomea produces anti-angiogenic effects by inhibiting the VEGFR2 signaling pathway.
药用蘑菇密纹薄孔菌已被用于治疗癌症，但它的抗血管生成作用尚未得到详细研究。
本研究的主要目的是确定密纹薄孔菌抗血管生成作用的活性的分子机制。
在体外研究了密纹薄孔菌乙醇提取物（ACEE）对内皮细胞迁移和微血管形成的影响，并在体内用 Matrigel plugs 植入小鼠模型中进行了研究。使用 Western blot 检测细胞内信号通路的激活情况。在小鼠肺转移模型中，通过免疫组织化学评估蛋白质表达。
我们表明，ACEE 处理抑制了人脐静脉内皮细胞（HUVEC）的细胞迁移和管形成。ACEE 抑制了血管内皮生长因子受体 2（VEGFR2）的磷酸化和血管内皮生长因子（VEGF）处理的 HUVEC 中促血管生成激酶的表达，此外还降低了 Janus 激酶 2（JAK2）的表达和信号转导和转录激活因子 3（STAT3）的磷酸化。ACEE 处理抑制了体内 Matrigel plugs 中 VEGF 诱导的微血管形成。此外，ACEE 显著降低了 Lewis 肺癌细胞中 VEGFR2 的表达，并下调了小鼠肺转移中 CD31 和 VEGFR2 的表达。
这些结果表明，密纹薄孔菌通过抑制 VEGFR2 信号通路产生抗血管生成作用。
