Celastrus Orbiculatus Extract Inhibits Tumor Angiogenesis by Targeting Vascular Endothelial Growth Factor Signaling Pathway and Shows Potent Antitumor Activity in Hepatocarcinomas in Vitro and in Vivo

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.orbiculatus 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 C.orbiculatus was used.Mouse hepatic carcinoma cells (Hepa1-6) were treated with COE in different nontoxic concentrations(10,20,40,80,and 160μg/mL).The mRNA and protein expression levels of vascular endothelial growth factor(VEGF) were detected by reverse transcription-polymerase chain reaction(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 antiangiogenic effects.Results:COE significantly inhibited proliferation and induced apoptosis in Hepal -6 cells and inhibited VEGF expression at both 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 decreased tumor angiogenesis. Conclusions:In summary,COE could be used to treat hepatic carcinoma.The mechanisms of the antitumor activity of COE may be due to its effects against tumor angiogenesis by targeting the VEGF protein.