J Cancer 2018; 9(18):3366-3372. doi:10.7150/jca.25082

Research Paper

Dihydroartemisinin enhances VEGFR1 expression through up-regulation of ETS-1 transcription factor

Na Niu1,#, Changmei Yu2,3,#, Liqun Li3, Qiang Liu3, Wenqian Zhang4, Kaili Liang5, Youming Zhu5, Jing Li5, Xia Zhou6, Jinbao Tang2,✉, Ju Liu3,✉

1. Department of Pediatrics, Shandong Provincial Hospital Affiliated to Shandong University, 324 Jingwu Road, Jinan,Shandong, China 250021
2. College of Pharmacy, Weifang Medical University, 7166 Baotong West Street, Weifang, Shandong China 261053
3. Medical Research Center, Shandong Provincial Qianfoshan Hospital, Shandong University, 16766 Jingshi Road, Jinan, Shandong China 250014
4. College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China
5. College of Chemistry, Shandong Normal University, 88 Wenhua East Road, Jinan, Shandong China 250014
6. Department of Rehabilitation Medicine, The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China
# These authors contributed equally to the work

Abstract

Angiogenesis is required for tumor growth. Dihydroartemisinin (DHA), a the effective anti-malarial derivative of artemisinin, demonstrated potent anti-angiogenic activities that closely related to the regulation of vascular endothelial growth factor (VEGF) signaling cascade. VEGF receptor 1 (VEGFR1), a receptor in endothelial cells (ECs), coordinately regulate angiogenic activity triggered by ligand-receptor binding. Here we aimed to explore the effects of DHA on VEGFR1 expression in ECs. We found that DHA significantly increases VEGFR1 expression in human umbilical vein endothelial cells (HUVECs). In addition, DHA significantly upregulates the level of V-Ets Avian Erythroblastosis Virus E26 Oncogene Homolog 1 (ETS-1), a transcriptional factor which binds to the human VEGFR1 promoter. ChIP assay showed that DHA increases ETS-1 binding to the -52 ETS motif on the VEGFR1 promoter. Knockdown of ETS-1 by RNA interference abolished DHA-induced increase of VEGFR1 expression. Taken together, we demonstrated that DHA elevates VEGFR1 expression via up-regulation of ETS-1 transcription in HUVECs.

Keywords: dihydroartemisinin, angiogenesis, endothelial cells, VEGFR1, ETS-1

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.
How to cite this article:
Niu N, Yu C, Li L, Liu Q, Zhang W, Liang K, Zhu Y, Li J, Zhou X, Tang J, Liu J. Dihydroartemisinin enhances VEGFR1 expression through up-regulation of ETS-1 transcription factor. J Cancer 2018; 9(18):3366-3372. doi:10.7150/jca.25082. Available from http://www.jcancer.org/v09p3366.htm