Neoalbaconol inhibits angiogenesis and tumor growth by suppressing EGFR-mediated VEGF production
Neoalbaconol inhibits angiogenesis and tumor growth by suppressing EGFR-mediated VEGF production
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Neoalbaconol 通过抑制 EGFR 介导的 VEGF 产生来抑制血管生成和肿瘤生长
DOI：
10.1002/mc.22602
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发表时间：
2017-05-01
影响因子：
4.6
通讯作者：
Cao, Ya
中科院分区：
文献类型：
--
作者：
Yu, Xinfang;Li, Wei;Cao, Ya
新albaconol，来自Albatrellus confluens，在先前的研究中显示出抗癌活性，但其在血管生成中的作用尚不清楚。在这里，我们确定了neoalbaconol是否可以减弱血管生成以及它是如何发生的。结果表明，新白细胞醇能够抑制乳腺癌细胞的增殖，并诱导其凋亡。此外，新白细胞醇抑制血管内皮生长因子（VEGF）诱导的人脐血管内皮细胞（HUVECs）的增殖，迁移，侵袭和毛细血管样管形成在体外和减少肿瘤血管生成在体内。VEGF受体激活和下游信号转导级联激活被新白细胞醇抑制。此外，neoalbaconol阻断EGFR介导的VEGF产生。EGFR过表达逆转了新白细胞醇诱导的VEGF减少，证实了EGFR抑制在新白细胞醇抗血管生成中的重要性。此外，在体内乳腺癌异种移植模型中，新白细胞醇抑制肿瘤生长和肿瘤血管生成。总之，这些结果表明，新白细胞醇可以通过直接抑制血管内皮细胞和减少癌细胞中的促血管生成因子来抑制肿瘤血管生成和生长。
Neoalbaconol, derived from Albatrellus confluens, shows anti-cancer activities in the previously study, but its role in angiogenesis is unknown. Here, we determined whether neoalbaconol could attenuate angiogenesis and how does it occur. Data demonstrated that neoalbaconol could inhibit the proliferation of breast cancer cells and induce apoptosis. Also, neoalbaconol suppressed vascular endothelial growth factor (VEGF)-induced human umbilical vascular endothelial cells (HUVECs) proliferation, migration, invasion, and capillary-like tube formation in vitro and reduced tumor angiogenesis in vivo. VEGF receptor activation and the downstream signal transduction cascades activation were inhibited by neoalbaconol. Additionally, neoalbaconol blocked EGFR-mediated VEGF production. EGFR overexpression reversed the neoalbaconol-induced VEGF reduction, confirming the importance of the EGFR inhibition in anti-angiogenesis of neoalbaconol. Furthermore, neoalbaconol inhibited tumor growth and tumor angiogenesis in a breast cancer xenograft model in vivo. Taken together, these results indicate that neoalbaconol could inhibit tumor angiogenesis and growth through direct suppression effects on vascular endothelial cells and reduction of proangiogenic factors in cancer cells.