DADAG在体内外对血管生成的抑制作用

DADAG在体内外对血管生成的抑制作用

刘敬弢, 徐波, 李敏, 周瑛, 崔景荣^*

1. 北京大学医学部天然药物与仿生药物国家重点实验室, 北京 100191
2. 广西中医药研究院, 广西 530022

收稿日期:2010-03-02 修回日期:2010-04-15 出版日期:2010-05-15 发布日期:2010-05-15
通讯作者: 崔景荣*

Inhibition of angiogenesis by DADAG in vivo and in vitro

Jing-Tao Liu, Bo Xu, Min Li, Ying Zhou, Jing-Rong Cui^*

1. State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China
2. Traditional Chinese Medicine Institute of the Guangxi Zhuang Autonomous Region, Guangxi 530022, China

Received:2010-03-02 Revised:2010-04-15 Online:2010-05-15 Published:2010-05-15
Contact: Jing-Rong Cui*

摘要/Abstract

摘要： DADAG是一种糖醇烷基化的衍生物, 现已被证实具有抗肿瘤活性。通过鸡胚绒毛尿囊膜(CAM)模型以及人脐静脉内皮细胞(HUVEC)的增殖和迁移实验进一步发现DADAG有抗血管生成作用, 并且探讨了其可能的作用机制。实验结果显示, DADAG (100, 500和1000 μmol/L)可以浓度依赖地抑制CAM中的血管生成。在SRB实验中, DADAG (45, 90, 135, 180和225 μmol/L)可以抑制HUVEC的增殖, 并且也具有浓度和时间依赖性。为了在检测时有效排除细胞增殖对细胞迁移结果的影响, 运用高内涵实验证实了DADAG (45, 135和225 μmol/L)可以直接抑制HUVEC的运动。免疫荧光实验显示DADAG对血管生成的抑制作用可能是通过降低HUVEC中血管内皮细胞生长因子(VEGF)的表达实现的。总之, DADAG在体内及体外的抗血管生成作用与下调内皮细胞中VEGF的表达有关。

关键词: 血管生成, 鸡胚绒毛尿囊膜, 人脐静脉内皮细胞, 增殖, 迁移, 血管内皮细胞生长因子

Abstract: 1,2,5,6-Dianhydro-3,4-diacetyl-galactitol (DADAG), an alkylating sugar alcohol derivative, has been shown effective against tumor growth. In this research, we explored the effect of DADAG on angiogenesis in chick chorioallantoic membrane (CAM) model and on the proliferation and migration of human umbilical vein endothelial cells (HUVECs). We also studied the possible mechanism of the anti-angiogenesis effect of DADAG. The results showed that DADAG (100, 500 and 1000 μmol/L) inhibited angiogenesis in CAM model dose-dependently. Sulforhodamine B (SRB) assay indicated that DADAG (45, 90, 135, 180 and 225 μmol/L) suppressed HUVECs proliferation in a dose-dependent and time-dependent manner. High Content Screening (HCS, Cellomics) assay, in which the influence of cell proliferation on migration could be excluded, indicated that DADAG (45, 135 and 225 μmol/L) directly inhibited the motility of HUVECs. Immunofluorescence assay suggested that DADAG inhibited angiogenesis possibly by decreasing vascular endothelial growth factor (VEGF) expression in HUVECs. Our findings reveal that DADAG show anti-angiogenic activity in vivo and in vitro, which is related to the downregulation of VEGF expression in endothelial cells.

Key words: Angiogenesis, CAM, HUVEC, Proliferation, Migration, VEGF

中图分类号:

R965.11

Supporting: ^*Corresponding author. Tel./fax: 86-10-8282467

刘敬弢, 徐波, 李敏, 周瑛, 崔景荣^*. DADAG在体内外对血管生成的抑制作用[J]. .

Jing-Tao Liu, Bo Xu, Min Li, Ying Zhou, Jing-Rong Cui^* . Inhibition of angiogenesis by DADAG in vivo and in vitro[J]. .

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