Department of Surgery, Kaohsiung Armed Forces General Hospital, Kaohsiung 80284, Taiwan, R.O.C.
Medical Education Center, Kaohsiung Armed Forces General Hospital, Kaohsiung 80284, Taiwan, R.O.C.
Oncol Rep. 2018 May;39(5):2351-2357. doi: 10.3892/or.2018.6312. Epub 2018 Mar 14.
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.
抗血管生成是癌症化疗中最常见的临床障碍之一。山奈酚是一种在许多水果和蔬菜中发现的类黄酮植物化学物质。我们之前的研究表明，山奈酚通过 ROS 介导的 p53/ATM/死亡受体信号通路诱导人脐静脉内皮细胞（HUVEC）凋亡。然而，山奈酚的抗血管生成潜力尚不清楚，其在 VEGF 刺激的 HUVEC 中的潜在机制需要进一步探索。在本研究中，山奈酚显著降低了 VEGF 刺激的 HUVEC 活力。山奈酚处理还抑制了 VEGF 刺激的 HUVEC 中的细胞迁移、侵袭和管形成。Western blot 和激酶活性测定结果表明，山奈酚处理后 VEGF 刺激的 HUVEC 中 VEGFR-2 及其下游信号级联（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/VEGFR-2 及其下游信号级联（PI3K/AKT、MEK 和 ERK）在 VEGF 刺激的内皮细胞中具有抑制血管生成的作用。
