Dihydroartemisinin inhibits vascular endothelial growth factor-induced endothelial cell migration by a p38 mitogen-activated protein kinase-independent pathway.
Dihydroartemisinin (DHA), a semi-synthetic derivative of artemisinin, has been demonstrated to possess a strong antiangiogenic activity. However, the molecular mechanisms underlying this effect remain unclear. Endothelial cell (EC) migration is an essential component of angiogenesis, and the p38 mitogen-activated protein kinase (MAPK) signaling pathway plays a key role in the regulation of migration induced by vascular endothelial growth factor (VEGF). The aim of the present study was to investigate the effects of DHA on EC migration and the p38 MAPK signaling pathway. Human umbilical vein ECs (HUVECs) were treated with DHA and VEGF-induced migration was analyzed. The activation of p38 MAPK was detected by western blot analysis, and the migration assays were performed with a p38-specific inhibitor, SB203850. It was revealed that 20 μM DHA significantly reduced EC migration in the transwell migration assay, wound healing assay and electrical cell-substrate impedance sensing real-time analysis. However, DHA did not affect p38 MAPK phosphorylation or expression. In the absence or presence of SB203850, DHA induced a similar proportional reduction of EC migration in the three migration assays. Therefore, the present study demonstrated that DHA inhibits VEGF-induced EC migration via a p38 MAPK-independent pathway.
Laboratory of Microvascular Medicine, Medical Research Center, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong 250014, P.R. China ; Department of Cardiology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong 250014, P.R. China.
Ling
L
Guo
Laboratory of Microvascular Medicine, Medical Research Center, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong 250014, P.R. China.
Fengyun
F
Dong
Department of Cardiology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong 250014, P.R. China.
Yinglong
Y
Hou
Department of Emergency Medicine, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong 250014, P.R. China.
Weidong
W
Cai
Department of Traditional Chinese Medicine, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong 250014, P.R. China.
Xia
X
Zhou
Department of Nephrology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong 250014, P.R. China.
Ai-Ling
AL
Huang
Department of Orthopedics, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
Min
M
Yang
G.W. Hooper Research Foundation, University of California, San Francisco, CA 94143-0552, USA.
Thaddeus D
TD
Allen
Laboratory of Microvascular Medicine, Medical Research Center, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong 250014, P.R. China.
Ju
J
Liu
angiogenesis; dihydroartemisinin; endothelial cell; migration; p38 mitogen-activated protein kinase