中国动脉硬化杂志2017，Vol.25Issue(7)：655-660,6.
达沙替尼对人脐静脉内皮细胞的损伤与PI3K/Akt途径抑制有关
Inhibition of PI3K/Akt pathway involved in damaging of dasatinib to human umbilical vein endothelial cells
摘要
Abstract
Aim To explore the effect of dasatinib on proliferation,migration,cell cycle and apoptosis of human umbilical vein endothelial cells cytologically and molecularly to offer help on clinical application of dasatinib.Methods Experimental grouping:dasatinib group (dasatinib concentration was 50 nmol/L) and LY294002 group (PI3K inhibitor,concentration was 20 μmol/L),combined treatment group (dasatinib treatment concentration was 50 nmol/L,the concentration of LY294002 for 20 μmol/L) and mock group (DMSO was 0.1％).Cell viability was measured by CCK8.The migration ability of human umbilical vein endothelial cells was measured by scratch assay.Apoptosis and cell cycle were analyzed by flow cytometry.The expression and phosphorylation of Akt protein were determined by Western blot.Results The cell viability of human umbilical vein endothelial cells decreased gradually following the increasing concentration (1 ～ 400 nmol/L) and prolonged exposure to dasatinib (50 nmol/L,24 ～ 96 h).Dasatinib and LY294002 (an inhibitor of PI3K),both inhibited cell viability of human umbilical vein endothelial cells.Dasatinib (50～ 100 nmol/L) weakened the migration capability of human umbilical vein endothelial cells.In addition,compared with control,dasatinib (50 nmol/L) induced apoptosis and cell cycle arrest (P＜0.05) of human umbilical vein endothelial cells.The phosphorylation of Akt was inhibited by dasatinib and LY294002,and LY294002 had more powerful inhibition of p-Akt than dasatinib.Conclusion Dasatinib could facilitate the injures of human umbilical vein endothelial cells via PI3K/Akt pathway,mainly to suppress the proliferation and migration of human umbilical vein endothelial cells,alter the cell morphology,blocked the G1-S transition and induced apoptosis.关键词
达沙替尼/细胞增殖/细胞迁移/细胞凋亡/细胞周期/PI3K/Akt途径Key words
Dasatinib/Cell proliferation/Cell migration/Apoptosis/Cell cycle/PI3K/Akt pathway分类
医药卫生引用本文复制引用
王茜,周兆,张雷,吕林林,刘革修..达沙替尼对人脐静脉内皮细胞的损伤与PI3K/Akt途径抑制有关[J].中国动脉硬化杂志,2017,25(7):655-660,6.基金项目
国家自然科学基金项目(81270568) （81270568）
