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

Publication date: Available online 24 December 2019Source: Life SciencesAuthor(s): Peng Gao, Li-li Wang, Jing Liu, Fengyun Dong, Wei Song, Lin Liao, Bei Wang, Wenqian Zhang, Xia Zhou, Qi Xie, Rong Sun, Ju LiuAbstractAimsEndothelial 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 methodsHuman 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 findingsDHA 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 co...
Source: Life Sciences - Category: Biology Source Type: research