柠檬苦素调控Tiam1基因表达影响人体血管瘤内皮细胞VEGF/VEGFR2通路及诱导其凋亡的机制研究  

Limonin effected VEGF/VEGFR2 pathway and induced apoptosis in human hemangioma endothelial cells by regulating expression of Tima1 gene

作　　者：李立佳 符梅竹[1] 黄惠敏 郑诗华 阎青青 张晓钿[1,2] LI Li-Jia;FU Mei-Zhu;HUANG Hui-Min;ZHENG Shi-Hua;YAN Qing-Qing;ZHANG Xiao-Dian(Department of Pediatrics,First Affiliated Hospital of Hainan Medical College,Haikou 570102,China)

机构地区：[1]海南医学院第一附属医院儿科,海口570102 [2]海南医学院海南省药物安全性评价研究中心,海口571199

出　　处：《中国免疫学杂志》2020年第6期723-728,共6页Chinese Journal of Immunology

基　　金：海南省卫生计生行业科研项目(No.16A200012)。

摘　　要：目的:研究柠檬苦素Toonaciliatin A对血管瘤内皮细胞(HemEC)增殖、凋亡的影响及潜在作用机制。方法:胶原蛋白酶A分离HemEC细胞,MTT法测定不同浓度Toonaciliatin A对HemEC细胞生存率的影响,流式细胞术测定HemEC细胞凋亡率,Western blot检测蛋白表达,qRT-PCR检测RNA的表达。结果:Toonaciliatin A能够抑制HemEC增殖,促进HemEC细胞凋亡;Toonaciliatin A抑制Tiam1蛋白表达,过表达Tiam1逆转了Toonaciliatin A对HemEC的抑制作用;Toonaciliatin A能够抑制VEGF和VEGFR2蛋白表达,过表达Tiam1逆转了Toonaciliatin A对VEGF和VEGFR2蛋白表达的抑制作用。结论:柠檬苦素类似物Toonaciliatin A通过靶向Tiam1基因抑制VEGF/VEGFR2通路抑制HemEC细胞增殖,促进细胞凋亡。Objective:To investigate the effects of Limonin on proliferation and apoptosis of hemangioma endothelial cells(HemEC)and its underlying mechanism.Methods:HemEC cells were separated by collagenase A.Survival rate of HemEC treated with different dose of Toonaciliatin A was determined by MTT assay.Apoptotic rate of HemEC cells was measured by flow cytometry.Expression levels of proteins were detected by Western blot.Expression levels of RNA was detected by qRT-PCR.Results:Toonaciliatin A inhibited the proliferation and induced apoptosis in HemEC.Toonaciliatin A inhibited the expression levels of Tiam1 in HemEC.Overexpression of Tiam1 reversed the inhibitory effect of Toonaciliatin A on HemEC.Toonaciliatin A inhibited the expression of VEGF and VEGFR2.Overexpression of Tiam1 reversed the inhibitory effect of Toonaciliatin A on the expression of VEGF and VEGFR2.Conclusion:Toonaciliatin A-one of limonoids,inhibits the proliferation and reduced cell apoptosis in HemEC by targeting Tiam1 gene to inhibit the VEGF/VEGFR2 pathway.

关 键 词：柠檬苦素类似物 血管瘤内皮细胞 T淋巴瘤侵袭转移诱导基因 血管内皮生长因子/血管内皮生长因子受体2 增殖 凋亡 

分 类 号：R739[医药卫生—肿瘤]