PI3K/Akt抑制剂CCT128930抑制人脐静脉血管内皮细胞增殖与血管生成的实验研究  

Inhibitor of PI3K/Akt,CCT128930,suppresses proliferation and tube formation of human umbilical vein endothelial cells

作　　者：费洪荣[1] 许广群[2] 朱永平[3] 史仁玖[3] 王德才[3] 王凤泽[3] 

机构地区：[1]泰山医学院药学院,山东泰安271016 [2]泰山医学院基础医学院,山东泰安271016 [3]泰山医学院生物科学学院,山东泰安271016

出　　处：《中国药理学通报》2012年第10期1413-1416,共4页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 30800422);山东省自然科学基金资助项目(No ZR2011HQ034)

摘　　要：目的探讨一类新的PI3K/Akt抑制剂CCT128930对人脐静脉血管内皮细胞(HUVEC)增殖与血管生成的影响。方法采用MTT法检测CCT128930对HUVEC存活的影响;流式细胞术分析细胞周期变化;AnnexinⅤ-FITC试剂盒检测细胞凋亡;体外小管形成实验观察CCT128930对HUVEC体外小管形成的影响;免疫印迹法检测蛋白表达水平。结果CCT128930可通过阻滞细胞于G1期而抑制HUVEC的增殖,且抑制作用呈剂量依赖性,但对HUVEC的凋亡无影响;HUVEC经CCT128930处理后,体外小管形成能力受到明显抑制;低浓度的CCT128930抑制内皮细胞中VEGF的表达,但对Akt的磷酸化水平无影响。结论 CCT128930能够抑制HUVEC的增殖与血管生成,其抑制血管生成活性可能与其调控VEGF的表达水平相关。Aim To assess the effects of CCT128930,an inhibitor of Akt,on cell proliferation and angiogenesis in cultured human umbilical vein endothelial cells（HUVECs） in vitro.Methods Cell viability was detected by MTT assay,cell cycle was analyzed by flow cytometry,AnnexinⅤ-FITC apoptosis detection kit was used to detect apoptosis of cells,and protein expression was examined by Western blot.Results MTT and cell cycle analysis results indicated that CCT128930 inhibited the growth of HUVECs in a dose-dependent manner,and arrested cell cycle progression at the G1 phase.In addition,tube formation of HUVECs was markedly inhibited by CCT128930.Western blot results showed that anti-tube formation activity of lowdose CCT128930 was not related with the PI3K / Akt pathway,and suppressing the expression of VEGF in HUVECs may be invlolved in this process.Conclusion CCT128930 exerts anti-angiogenic activity in HUVECs and the inhibition of VEGF expression potentially contributes to its anti-angiogenic activity.

关 键 词：脐静脉血管内皮细胞 CCT128930 PI3K Akt 细胞增殖 血管生成 血管内皮生长因子 

分 类 号：R322.123[医药卫生—人体解剖和组织胚胎学] R329.24[医药卫生—基础医学]