Kaempferol inhibits angiogenic ability by targeting VEGF receptor-2 and downregulating the PI3K/AKT, MEK and ERK pathways in VEGF-stimulated human umbilical vein endothelial cells
Kaempferol inhibits angiogenic ability by targeting VEGF receptor-2 and downregulating the PI3K/AKT, MEK and ERK pathways in VEGF-stimulated human umbilical vein endothelial cells
复制标题
DOI：
10.3892/or.2018.6312
复制
发表时间：
2018-05-01
期刊：
影响因子：
4.2
通讯作者：
Yang, Jai-Sing
中科院分区：
文献类型：
--
作者：
Chin, Hsien-Kuo;Horng, Chi-Ting;Yang, Jai-Sing
抗血管生成是癌症化疗中最常见的临床障碍之一。山奈酚是一种黄酮类植物化学物质，存在于许多水果和蔬菜中。我们之前的研究表明，山奈酚通过 ROS 介导的 p53/ATM/死亡受体信号触发人脐静脉内皮细胞 (HUVEC) 细胞凋亡。然而，山奈酚的抗血管生成潜力仍不清楚，其潜在机制值得在 VEGF 刺激的 HUVEC 中进一步探索。在本研究中，山奈酚显着降低 VEGF 刺激的 HUVEC 活力。山奈酚治疗还抑制 VEGF 刺激的 HUVEC 中的细胞迁移、侵袭和管形成。在用山奈酚处理后，在 VEGF 刺激的 HUVEC 中通过蛋白质印迹和激酶活性测定确定 VEGF 受体 2 (VEGFR-2) 及其下游信号级联（例如 AKT、mTOR 和 MEK1/2-ERK1/2）减少。本研究表明，山奈酚可能通过调节 VEGF 刺激的内皮细胞中的 VEGF/VEGFR-2 及其下游信号级联（PI3K/AKT、MEK 和 ERK）来抑制血管生成。
Anti-angiogenesis is one of the most general clinical obstacles in cancer chemotherapy. Kaempferol is a flavonoid phytochemical found in many fruits and vegetables. Our previous study revealed that kaempferol triggered apoptosis in human umbilical vein endothelial cells (HUVECs) by ROS-mediated p53/ATM/death receptor signaling. However, the anti-angiogenic potential of kaempferol remains unclear and its underlying mechanism warranted further exploration in VEGF-stimulated HUVECs. In the present study, kaempferol significantly reduced VEGF-stimulated HUVEC viability. Kaempferol treatment also inhibited cell migration, invasion, and tube formation in VEGF-stimulated HUVECs. VEGF receptor-2 (VEGFR-2), and its downstream signaling cascades (such as AKT, mTOR and MEK1/2-ERK1/2) were reduced as determined by western blotting and kinase activity assay in VEGF-stimulated HUVECs after treatment with kaempferol. The present study revealed that kaempferol may possess angiogenic inhibition through regulation of VEGF/VEGFR-2 and its downstream signaling cascades (PI3K/AKT, MEK and ERK) in VEGF-stimulated endothelial cells.