A Sphingosine Kinase-1 Inhibitor, SKI-II, Induces Growth Inhibition and Apoptosis in Human Gastric Cancer Cells

SKI-II has been reported as an inhibitor of sphingosine kinase 1 and has been extensively used to prove theinvolvement of sphingosine kinase and sphingosine-1-phosphate (Sphk1) in cellular processes. In the currentstudy, we investigated the effects of SKI-II and its potential mechanisms in human gastric cancer SGC7901cells. After treatment with SKI-II, cell growth, cell cycle distribution, apoptosis, expression of Sphk1, NF-κB,Bcl-2, Bax and p27 were assessed by MTT assay, flow cytometry, electron microscopy, immunocytochemistryand Western-blot assay, respectively. Our results showed that SKI-II markedly inhibited SGC7901 cell survivalin a dose-dependent manner, reduced cell proliferation with accumulation of cells in the G0/G1 phase andinduced apoptosis in the tumor cells. Furthermore, Western blotting and immunocytochemistry showed that theexpression of p27 and Bax was increased significantly, but the expression of NF-κB, Bcl-2 and Sphk1 decreasedby different degrees. These results indicate that SKI-II induced cell growth arrest and apoptosis. The increasedapoptotic sensitivity of SGC7901 was correlated with NF-κB or Bcl-2/Bax activation.