Zhang Cai-Xia, Liu Hong, Gong Yu-Yan, He Hong-Wei, Shao Rong-Guang
Yao Xue Xue Bao. 2014 Feb;49(2):204-8.
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 G1-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.
鞘氨醇激酶1(SphK1)在细胞生物学功能中发挥关键作用。在此,我们研究了SphK1抑制剂SKI II对肝癌HepG2细胞周期进程和侵袭的影响。通过SRB法测定细胞存活率,通过流式细胞术检测细胞周期进程,通过基质胶-Transwell法测量细胞侵袭能力,并通过蛋白质印迹法检测蛋白质表达。结果表明,SKI II以剂量依赖性方式显著抑制HepG2细胞存活,诱导HepG2细胞G1期阻滞并抑制细胞侵袭。SKI II显著降低了G1期相关蛋白CDK2、CDK4和Cdc2的表达以及细胞侵袭相关蛋白MMP2和MMP9的水平。结果表明,SKI II抑制细胞周期进程和细胞侵袭,这意味着SphK1是肝癌治疗的潜在靶点。