Dihydroartemisinin inhibits endothelial cell tube formation by suppression of the STAT3 signaling pathway.

Abstract

AIMS:

Endothelial cell (EC) tube formation is crucial for tumor angiogenesis, which becomes a target for chemotherapy. The anti-malaria agent dihydroartemisinin (DHA) inhibited tumor growth and angiogenesis. The aim of this study was to investigate the effects of DHA on EC tube formation and the underlying mechanisms.

MATERIALS AND METHODS:

Human umbilical vein endothelial cells (HUVECs) were cultured with different concentrations of DHA, and the tube formation was measured by in vitro angiogenesis assay. The protein levels of signal transducer and activator of transcription factor 3 (STAT3), phosphorylated STAT3 and fatty acid synthase (FASN) were detected by Western blotting. The gene expression of FASN was determined by real time-polymerase chain reaction (RT-PCR). The FASN siRNA and STAT3 (Y705D) vector were introduced into HUVECs by lipofectin transfection.

KEY FINDINGS:

DHA treatment inhibited tube formation, and the phosphorylation of STAT3 on Y705 of HUVECs. The expression of FASN was down-regulated by DHA and STAT3 inhibitor. The inhibitory effect of DHA on FASN expression in HUVECs was eliminated by co-treatment with the STAT3 inhibitor. Over-expression of STAT3 (Y705D) relieved the inhibitory effect of DHA on tube-formation and FASN expression. Under hypoxia condition, expression of FASN was up-regulated but inhibited by DHA treatment in HUVECs through suppression of STAT3 phosphorylation.

SIGNIFICANCE:

We demonstrate that DHA inhibits the protein level of FASN via attenuation of the Y705 phosphorylation of STAT3, and subsequently inhibits tube formation of HUVECs. Our results support the therapeutic potential of DHA on angiogenesis.

• Authors: Peng Gao, Li-Li Wang, Jing Liu, Fengyun Dong, Wei Song, Lin Liao, Bei Wang, Wenqian Zhang, Xia Zhou, Qi Xie, Rong Sun, Ju Liu
• Journal: Life sciences (Life Sci) Vol. 242 Pg. 117221 (Feb 01 2020) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 31881224 (Publication Type: Journal Article)
• Copyright: Copyright © 2019. Published by Elsevier Inc.

Chemical References

• Angiogenesis Inhibitors
• Artemisinins
• STAT3 Transcription Factor
• STAT3 protein, human
• artenimol
• Fatty Acid Synthases

Topics

• Angiogenesis Inhibitors (pharmacology)
• Artemisinins (pharmacology)
• Cell Differentiation (drug effects)
• Dose-Response Relationship, Drug
• Fatty Acid Synthases (metabolism)
• Gene Expression (drug effects)
• Human Umbilical Vein Endothelial Cells (drug effects)
• Humans
• Hylobatidae
• Neovascularization, Physiologic (drug effects)
• Real-Time Polymerase Chain Reaction
• STAT3 Transcription Factor (antagonists & inhibitors, metabolism)
• Signal Transduction (drug effects)