PI3Kα抑制剂BYL719抑制脐静脉血管内皮细胞增殖及血管生成的研究  

Inhibitor of PI3Kα, BYL719 Suppresses Proliferation and Tube Formation of Human Umbilical Vein Endothelial Cells

作　　者：王西双 庄梦玮 姜文艳[1] 张翠[1] 王凤泽[1] 

机构地区：[1]泰山医学院生命科学学院,山东泰安271016

出　　处：《中国现代应用药学》2015年第12期1419-1423,共5页Chinese Journal of Modern Applied Pharmacy

基　　金：国家自然科学基金资助项目(81272683)

摘　　要：目的探讨PI3Kα抑制剂BYL719对人脐静脉血管内皮细胞(human umbilical vein endothelial cells,HUVEC)增殖与血管生成的影响。方法采用MTT法测定BYL719对HUVEC活力的抑制作用;用流式细胞术检测BYL719对其细胞周期的影响;体外小管形成实验观察BYL719对血管生成的影响;Western blot检测Akt、p-Akt、cyclin D1和CDK4蛋白表达水平的变化。结果 BYL719抑制了HUVEC中Akt的磷酸化水平;BYL719作用细胞后,HUVEC的细胞活力显著降低;BYL719能够通过下调cyclin D1和CDK4的表达而阻滞细胞于G1期,进而抑制HUVEC的增殖;HUVEC经BYL719处理后,体外小管形成能力受到显著抑制。结论 BYL719降低了HUVEC中Akt的磷酸化水平,能够抑制HUVEC的细胞增殖和血管生成。OBJECTIVE To assess the effects of BYL719, an inhibitor of PI3K？, on cell proliferation and angiogenesis in cultured human umbilical vein endothelial cells（HUVEC） in vitro. METHODS Cell viability was detected by MTT assay. Cell cycle was analyzed by flow cytometry. The expression of Akt, p-Akt, cyclin D1 and CDK4 was examined by Western blot analysis. RESULTS BYL719 inhibited the phosphorylation of Akt in HUVEC. MTT results indicated that BYL719 inhibited the growth of HUVEC in a dose-dependent manner. BYL719 decreased the expression of cyclin D1 and CDK4, and arrested cell cycle progression at the G1 phase. In addition, tube formation of HUVECs was markedly inhibited by BYL719. CONCLUSION BYL719 inhibits the growth and exerts anti-angiogenic activity in HUVEC.

关 键 词：人脐静脉血管内皮细胞 BYL719 PI3Kα 细胞增殖 细胞周期 血管生成 

分 类 号：R965.2[医药卫生—药理学]