乙二酰二脱水卫矛醇对小鼠移植性肝癌H_(22)肿瘤生长和血管生成的抑制作用  

Inhibitory effect of diacetyldianhydrogalactitol on transplanted hepatocarcinoma 22 growth and angiogenesis in mice

作　　者：刘敬弢[1] 郭维[1] 徐波[1] 佟侃[1] 周瑛[2] 崔景荣[1] 

机构地区：[1]北京大学药学院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,南宁530022

出　　处：《中国新药杂志》2011年第2期115-119,共5页Chinese Journal of New Drugs

基　　金：重大新药创制科技重大专项(2009ZX09301-010)

摘　　要：目的:研究乙二酰二脱水卫矛醇(DADAG)在体内对肿瘤生长和血管生成的抑制作用及其机制。方法:采用小鼠H22模型观察DADAG对肿瘤生长的影响;免疫组化和W estern blot法分别检测DADAG对肿瘤组织中微血管密度(MVD)和血管内皮生长因子(VEGF)以及转录因子Sp1表达的影响。结果:DAD-AG(5和10 mg.kg-1.d-1)可以浓度依赖性地降低小鼠瘤重(抑制率分别为29.8%和60.2%)和MVD(抑制率分别为38.9%和66.7%),引起肿瘤组织坏死,降低VEGF及Sp1的表达量,但无明显肝、肾毒性。结论:DADAG可以抑制小鼠H22移植瘤的生长和血管生成,下调VEGF及Sp1的表达是其可能的作用机制之一。Objective： To explore the anti-tumor and anti-angiogenesis effect of diacetyldianhydrogalactitol（DADAG） on hepatocarcinoma H22 in mice and the possible mechanism.Methods： Solid-type hepatocarcinoma H22 was transplanted in mice to observe the inhibitory effect of DADAG on tumor growth.Immunohistochemical staining and western blot were performed to detect the effect of DADAG on microvessel density（MVD）,and the expression of vascular endothelial growth factor（VEGF） and its upstream transcription factor Sp1 in tumor tissues.Results： DADAG（5 and 10mg·kg-1·d-1） dose-dependently inhibited tumor growth by 29.8% and 60.2%,and MVD by 38.9% and 66.7%,respectively.DADAG also induced tumor necrosis and down-regulated the expression of VEGF and Sp1 without significant hepatotoxicity and nephrotoxicity.Conclusion： DADAG inhibits tumor growth and angiogenesis of hepatocarcinoma H22 in mice by decreasing VEGF and Sp1 expression.

关 键 词：乙二酰二脱水卫矛醇 肝癌H22 血管生成 微血管密度 

分 类 号：R979.1[医药卫生—药品]