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

被引：71

作者：

Chin, Hsien-Kuo ^{[1
]}

Horng, Chi-Ting ^{[2
,3
]}

Liu, Yi-Shan ^{[4
,5
]}

Lu, Chi-Cheng ^{[6
]}

Su, Chen-Ying ^{[7
]}

Chen, Pei-Syuan ^{[8
]}

Chiu, Hong-Yi ^{[6
]}

Tsai, Fuu-Jen ^{[9
,10
,11
]}

Shieh, Po-Chuen ^{[8
]}

Yang, Jai-Sing ^{[12
]}

机构：

[1] Kaohsiung Armed Forces Gen Hosp, Dept Surg, Kaohsiung 80284, Taiwan

[2] Kaohsiung Armed Forces Gen Hosp, Med Educ Ctr, Kaohsiung 80284, Taiwan

[3] Chung Shan Med Univ, Inst Biochem & Biotechnol, Taichung 40201, Taiwan

[4] E Da Hosp, Dept Dermatol, Kaohsiung 82445, Taiwan

[5] I Shou Univ, Kaohsiung 82445, Taiwan

[6] Buddhist Tzu Chi Gen Hosp, Dept Pharm, Hualien 97002, Taiwan

[7] Tajen Univ, Dept Nursing, Pingtung 90741, Taiwan

[8] Tajen Univ, Dept Pharm, 20 Weixin Rd, Pingtung 90741, Taiwan

[9] China Med Univ Hosp, Dept Med Res, Huamn Genet Ctr, Taichung 40447, Taiwan

[10] China Med Univ Hosp, Dept Med Genet, Taichung 40447, Taiwan

[11] China Med Univ, Sch Chinese Med, Taichung 40402, Taiwan

[12] China Med Univ, China Med Univ Hosp, Dept Med Res, 2 Yude Rd, Taichung 40447, Taiwan

来源：

ONCOLOGY REPORTS | 2018年 / 39卷 / 05期

关键词：

angiogenesis; kaempferol; VEGF receptor-2; AKT; MEK; ERK; human umbilical vein endothelial cells (HUVECs); CANCER STEM-CELLS; NF-KAPPA-B; INDUCED APOPTOSIS; AUTOPHAGY; MIGRATION; THERAPY; MODULATION; ARREST; AKT; CHEMOPREVENTION;

D O I：

10.3892/or.2018.6312

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：2351 / 2357

页数：7

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