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

  • Li, Pei-Hua (Department of Otorhinolaryngology, Affiliated Hospital of Xuzhou Medical College) ;
  • Wu, Jin-Xia (Jiangsu Key Laboratory of Biological Cancer Therapy, Xuzhou Medical College) ;
  • Zheng, Jun-Nian (Jiangsu Key Laboratory of Biological Cancer Therapy, Xuzhou Medical College) ;
  • Pei, Dong-Sheng (Jiangsu Key Laboratory of Biological Cancer Therapy, Xuzhou Medical College)
  • Published : 2015.01.06

Abstract

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

Keywords

Sphingosine kinase 1;SKI-II;proliferation;apoptosis;SGC7901 gastric cancer cells

Acknowledgement

Supported by : National Natural Science Foundation of China

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