Dihydroartemisinin inhibits endothelial cell migration via the TGF‑β1/ALK5/SMAD2 signaling pathway

Guo,Ling; Wen,Xiaoqing; Hou,Yinglong; Sun,Rong; Zhang,Liang; Liu,Fuhong; Liu,Ju

doi:10.3892/etm.2021.10141

Dihydroartemisinin inhibits endothelial cell migration via the TGF‑β1/ALK5/SMAD2 signaling pathway

Authors:
- Ling Guo
- Xiaoqing Wen
- Yinglong Hou
- Rong Sun
- Liang Zhang
- Fuhong Liu
- Ju Liu
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Affiliations: Department of Cardiology, Shandong Provincial Qianfoshan Hospital, Shandong Medicine and Health Key Laboratory of Cardiac Electrophysiology and Arrhythmia, Shandong University, Jinan, Shandong 250014, P.R. China, Department of Clinical Medicine, Weifang Medical University, Weifang, Shandong 261042, P.R. China, Advanced Medical Research Institute, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250014, P.R. China, Shandong Provincial Key Laboratory of Animal Resistance Biology, Institute of Biomedical Sciences, College of Life Sciences, Shandong Normal University, Jinan, Shandong 250014, P.R. China, Laboratory of Microvascular Medicine, Medical Research Center, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong 250014, P.R. China
Published online on: May 3, 2021 https://doi.org/10.3892/etm.2021.10141
Article Number: 709
Copyright: © Guo et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Anti‑angiogenesis therapy is a novel treatment method for malignant tumors. Endothelial cell (EC) migration is an important part of angiogenesis. Dihydroartemisinin (DHA) exhibits strong anti‑angiogenic and anti‑EC migration effects; however, the underlying molecular mechanisms are yet to be elucidated. The TGF‑β1/activin receptor‑like kinase 5 (ALK5)/SMAD2 signaling pathway serves an important role in the regulation of migration. The present study aimed to explore the effects of DHA treatment on EC migration and the TGF‑β1/ALK5/SMAD2 signaling pathway. The effects of DHA on human umbilical vein EC migration were assessed using wound healing and Transwell assays. The effects of DHA on the TGF‑β1/ALK5/SMAD2 signaling pathway were detected using western blotting. DHA exhibited an inhibitory effect on EC migration in the wound healing and Transwell assays. DHA treatment upregulated the expression levels of ALK5 and increased the phosphorylation of SMAD2 in ECs. SB431542 rescued the inhibitory effect of DHA during EC migration. DHA inhibited EC migration via the TGF‑β1/ALK5/SMAD2‑dependent signaling pathway, and DHA may be a novel drug for the treatment of patients with malignant tumors.

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