Antiangiogenic effect of celastrol on the growth of human glioma： an in vitro and in vivo study

作     者：ZHOU You-xin HUANG Yu-lun 

作者机构：Department of Neurosurgery the First Affiliated Hospital of Soochow University Suzhou Jiangsu 215006 China 

出 版 物：《Chinese Medical Journal》 (中华医学杂志（英文版）)

年 卷 期：2009年第122卷第14期

页      面：1666-1673页

核心收录：

学科分类：0710[理学-生物学] 1002[医学-临床医学] 07[理学] 08[工学] 09[农学] 071007[理学-遗传学] 0901[农学-作物学] 0836[工学-生物工程] 090102[农学-作物遗传育种] 

基　　金：Jiangsu Province Key Discipline Fund [XK200722] 

主　　题：angiogenesis celastrol glioma vascular endothelial growth factor 

摘      要：Background Celastrol is a major active component of Tripterygium wilfordii named ＂Thunder God Vine＂, which is widely used to treat rheumatoid arthritis in China. The present study aims to demonstrate that celastrol has potent anticancer activity against glioma in vitro and in vivo. Methods Proliferation, migration, and tube formation of ECV-304 cells were determined by MTT and matrigel assays. The antiangiogenesis effect of celastrol was assessed by the chick chorioallantoic membrane assay and the in vivo matrigel plug assay. Tumor microvessels （MVD） were determined immunohistochemically with anti-CD34 antibody. Vascular endothelial growth factor （VEGF） expression was defined as positive if distinct staining of the cytoplasm was observed in at least 10% of tumor cells at the deepest invasive site, central portion and superficial part of the tumor. MVD was estimated by averaging the counts of three times at a ×200 field in the most vascularized area of the deepest invasive site. Results Celastrol purified from T. wilfordiiinhibited the proliferation of vascular endothelial cells （ECV-304） with an IC50 value of 1.33 μg/ml. Celastrol, at the concentration of 0.2 μg/ml, significantly inhibited cell migration and tube formation. Celastrol inhibited angiogenesis in a dose-dependent manner both in vitro and in vivo. Subcutaneous administration of celastrol 5 days a week for 4 consecutive weeks significantly reduced tumor volume in a dose-dependent manner in the SHG-44 xenograff model. Celastrol at each different dose level lowered the density of MVD significantly in tumor bearing nude mice compared to the control group. Immunohistochemistry experiments further revealed that celastrol also decreased the level of VEGFR-1 and VEGFR-2 expression, but not the level of VEGF expression. Conclusions Celastrol elicits antiangiogenic effects in vitro and in vivo, and could be of potential use in the treatment of malignant cancers such as glioblastoma.