title: A sphingosine kinase-1 inhibitor, SKI-II, induces growth inhibition and apoptosis in human gastric cancer cells.
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-κB, 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-κB, 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-κB or Bcl-2/Bax activation.
authors.affiliation: Department of Otorhinolaryngology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, China E-mail : dspei@xzmc.edu.cn; jnzheng@xzmc.edu.cn.
authors.forename: Pei-Hua
authors.initials: PH
authors.lastname: Li
authors.forename: Jin-Xia
authors.initials: JX
authors.lastname: Wu
authors.forename: Jun-Nian
authors.initials: JN
authors.lastname: Zheng
authors.forename: Dong-Sheng
authors.initials: DS
authors.lastname: Pei
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000187:drug effects / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000187:drug effects / Q000378:metabolism; D013274:Stomach Neoplasms / Q000378:metabolism*; D013844:Thiazoles / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000187:drug effects / Q000378:metabolism; D000099157:Sphingosine Kinase
chemical_list: D016328:NF-kappa B; D017853:Phosphotransferases (Alcohol Group Acceptor); D018809:Proliferating Cell Nuclear Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D013844:Thiazoles; D051028:bcl-2-Associated X Protein; D000099157:Sphingosine Kinase; C525025:4-(4-(4-chloro-phenyl)thiazol-2-ylamino)phenol; C000595707:BCL2 protein, human; C413374:p27 antigen