SphK1抑制剂SKI Ⅱ抑制肝癌HepG2细胞周期及细胞侵袭  

Inhibitions of SphK1 inhibitor SKI II on cell cycle progression and cell invasion of hepatoma HepG2 cells

作　　者：张彩霞[1] 刘虹[1] 宫玉艳[1] 何红伟[1] 邵荣光[1] 

机构地区：[1]中国医学科学院、北京协和医学院医药生物技术研究所,北京100050

出　　处：《药学学报》2014年第2期204-208,共5页Acta Pharmaceutica Sinica

基　　金：国家重点基础研究发展计划(973计划)资助项目(2009CB52180);国家重大新药创制项目(2012ZX09301-002);国家自然科学基金资助项目(30701011,81273554)

摘　　要：鞘氨醇激酶1(sphingosine kinase 1,SphK1)在调控细胞基本生物学功能方面发挥重要作用,本研究考察了SphK1抑制剂SKI II对肝癌细胞HepG2周期及侵袭的影响。采用SRB方法检测细胞存活率,流式细胞仪检测细胞周期分布,Matrigel-Transwell方法检测细胞侵袭能力,Western blotting检测蛋白表达变化。结果表明,SKI II能够抑制HepG2细胞的存活,诱导HepG2细胞发生G1期阻滞以及抑制HepG2细胞的侵袭;SKI II能降低细胞G1期相关蛋白CDK2、CDK4以及Cdc2的表达水平,同时降低与细胞侵袭相关的MMP2和MMP9的蛋白水平。结果提示,SphK1抑制剂SKI II能引起细胞G1期阻滞及降低细胞侵袭能力,提示SphK1可能成为肝癌治疗的一个潜在靶点。Sphingosine kinase 1 （SphK1） plays critical roles in cell biological functions. Here we investigated the effects of SphK1 inhibitor SKI II on hepatoma HepG2 cell cycle progression and invasion. Cell survival was determined by SRB assay, cell cycle progression was assayed by flow cytometry, the ability of cell invasion was measured by Matrigel-Transwell assay and protein expression was detected by Western blotting. The results showed that SKI II markedly inhibited HepG2 cell survival in a dose-dependent manner, induced G1 phase arrest in HepG2 cell and inhibited cell invasion. SKI II markedly decreased the expressions of G^-phase-related proteins CDK2, CDK4 and Cdc2 and the levels of cell invasion-associated proteins MMP2 and MMP9. The results showed that SKI II inhibited cell cycle progression and cell invasion, implying SphK1 as a potential target for hepatoma treatment.

关 键 词：SphK1 SKI II 肝癌 HEPG2 细胞周期 侵袭 

分 类 号：R963[医药卫生—微生物与生化药学]