新型酪氨酸激酶抑制剂BSSD-1对斑马鱼血管生成及大肠癌HT29裸鼠肿瘤的抑制作用  

Inhibitory effect of a norel tyrosine kinase inhibitor BSSD-1 on angiogenesis of zebrafish embryo and tumor growth of HT-29 colon cancer xenografts in nude mice

作　　者：韩利文[1,2] 王思锋[1] 王加宁[1] 何秋霞[1] 陈贯虹[1] 袁延强[1] 陈锡强[1] 刘可春[1] 

机构地区：[1]山东省科学院生物研究所山东省生物传感器重点实验室,山东济南250014 [2]天津中医药大学中药学院,天津300193

出　　处：《中国药理学通报》2011年第10期1434-1438,共5页Chinese Pharmacological Bulletin

基　　金：山东省自然科学基金资助项目(NoSY2008C179);山东省科技发展计划资助项目(No2006GG3202038)

摘　　要：目的探讨化合物BSSD-1对斑马鱼新生血管的影响以及对大肠癌HT29裸鼠肿瘤的抑制作用。方法采用24hpf(hours post fertilization)健康TG(VEGFR2:GFP)系血管荧光转基因斑马鱼作为实验动物模型,加入不同剂量BSSD-1与胚胎共同孵育24 h,在荧光显微镜下观察背部节间血管(intersegmental vessels,ISV)生成情况,并计数评价抑制程度;进而建立人大肠癌HT29细胞裸小鼠模型,观察BSSD-1不同剂量作用下对裸鼠肿瘤的抑制作用,根据瘤体积及瘤重,计算相对肿瘤增殖率和肿瘤生长抑制率。结果化合物BSSD-1在0.25～25.0 mg·L-1范围抑制斑马鱼背部节间血管生成具有剂量相关性,12.5 mg·L-1抑制率可达98.8%;裸鼠肿瘤抑制试验中,大、中、小剂量组肿瘤生长抑制率试验结果分别为31.1%、40.0%和40.0%,统计学处理3组差异均有显著性。结论 BSSD-1可以抑制荷瘤裸鼠移植瘤的生长,该作用与抑制肿瘤新生血管生成有关。Aim To investigate inhibitory effect of BSSD-1 on angiogenesis zebrafish model and tumor growth of HT-29 colon cancer xenografts in nude mice.Methods Healthy transgenic zebrafish Tg（VEGFR2： GFP）at 24 hpf was used as animal model.Growth of intersegmental vessels（ISV） of larva trunk was scored under fluorescence microscope after different concentrations of BSDD-1 were added into medium of zebrafish and fertilized with zebrafish embryos for 24 h.Furthermore,the model of colonic cancer of nude mice were replicated by injecting HT29 colonic cancer cell subcutaneously.Every nude mouse was lavaged after the first injection for 27 d,and the relative tumor proliferation rates（RTV） and inhibition rates of tumor growth were counted based on the change of tumor volume and tumor weight of nude mice.Results BSSD-1 with the dose range of 0.25~25.0 mg·L-1 showed inhibition effect on angiogenesis of zebrafish model in the dose dependent manner,and the inhibition rate was up to 98.8% when its concentration was 12.5 mg·L-1.In the nude mice test,the inhibitory rate of three BSSD-1 groups were 31.1%,40.0% and 40.0%,respectively,and there were significant differences between BSSD-1 groups and model group.Conclusion The results show that BSSD-1 can obviously inhibit the growth of HT-29 colon cancer in nude mice,which is mediated by anti-angiogenesis effect.

关 键 词：BSSD-1 斑马鱼 抗肿瘤作用 节间血管 血管生成 HT29 大肠癌 

分 类 号：R-332[医药卫生] R322.12