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  

作　　者：钱亚云 张华 侯莹 员林 李国青 郭试瑜 Hisamits Tadashi 刘延庆 

机构地区：[1]Institute of Traditional Chinese Medicine and Western Medicine,School of Medicine,Yangzhou University [2]Department of Image,97th Hospital of People's Liberation Army [3]Department of Physiology,School of Medicine,Showa University,1-5-8 Hatanodai

出　　处：《Chinese Journal of Integrative Medicine》2012年第10期752-760,共9页中国结合医学杂志（英文版）

基　　金：Supported by Plans of Colleges and Universities in Jiangsu Province to Postgraduate Research and Innovation(No.CX09B-321Z);State Administration of Traditional Chinese Medicine of People's Republic of China(No.04-05ZP35)

摘　　要：Objective： Ce/astrus orbicu/atus 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 （Hepat-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 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.Objective： Ce/astrus orbicu/atus 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 （Hepat-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 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.

关 键 词：ANTITUMOR Celastrus orbiculatus Thunb. ANGIOGENESIS vascular endothelial growth factor 

分 类 号：R735.7[医药卫生—肿瘤]