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ABSTRACT Objective Celastrus orbiculatus Thunb has been used for thousands of years in China as a remedy against cancer and inflammatory diseases.This study aims to investigate whether C.orb iculatus extract (COE) could inhibit angiogenesis,which is the pivotal step in tumor growth,invasiveness,and metastasis.Methods In this study,the extract from the stem of Celastrus orbiculatus was used.Mouse hepatic carcinoma cells (Hepal-6) were treated with COE in different nontoxic concentrations (10,20,40,80,and 160 μg/mL).The mRNA and protein expression levels of vascular endothelial growth factor (VEGF) were detected by RT-PCR and Western Blot,respectively; the active fractions were further tested on C57BL/6 mice and human umbilical vein endothelial cells (HUVEC) for any anti-angiogenic effects.Results COE significantly inhibited proliferation and induced apoptosis in Hepal-6 cells and inhibited VEGF expression at both the mRNA and protein levels.Furthermore,this agent inhibited the formation of the capillary-like structure in primary cultured HUVEC in a dose-dependent manner.In vivo,COE significantly reduced the volume and weight of solid tumors with low adverse effects,and it decreased tumor angiogenesis.Conclusions In summary,COE could be used to treat hepatic carcinoma.The mechanisms of the antitumor activity of COE may possibly be due to its effects against tumor angiogenesis by targeting the VEGF protein.