title: [Effect of sphingosine kinase 1 on the apoptosis, migration and invasion of colon cancer HT-29 cells and its molecular mechanisms].
abstract: OBJECTIVE
  To investigate the effect of sphingosine kinase 1 (SphK1) on the proliferation, apoptosis, migration and invasion of colon cancer TH-29 cells and to explore its molecular mechanisms.
  
  
  METHODS
  Phorbol 12-myristate 13-acetate (PMA) was used to induce the activity of SphK1 and N, N-dimethylsphingosine (DMS) was used to suppress the activity of SphK1. Cell prolieration and apoptosis were detected by MTT assay and flow cytometry, respectively. The migration and invasion capabilities of the cells were assessed in Transwell chambers. The activity of SphK1 was assayed by autoradiography. Western blot was used to evaluate the protein expression of SphK1, p38, phosphorylated p38 (p-p38) and SAPK/JNK.
  
  
  RESULTS
  PMA and DMS were able to induce and suppress the activity and protein expression of SphK1 in a time-dependent manner, respectively. PMA enhanced and DMS suppressed the cell viability in a time- and dose-dependent manner. Being treated with 100 nmol/L PMA or 50 µmol/L DMS for 0, 6, 12, 24 h, the cell apoptosis rates of PMA group were (9.35 ± 0.84)%, (7.61 ± 0.48)%, (5.53 ± 0.76)% and (0.56 ± 0.33)%, contrastly, that of DMS group were (9.18 ± 0.94)%, (12.06 ± 1.41)%, (19.80 ± 2.36)% and (31.85 ± 3.60)%, respectively. Compared with the control group, the cell migration and invasion capabilities of the PMA group were significantly enhanced, and that of the DMS group were significantly suppressed. The migration cell number of control, PMA and DMS groups were 68.75 ± 6.15, 109.33 ± 11.63 and 10.83 ± 2.48, the invasion cell number of control, PMA and DMS groups were 55.42 ± 4.50, 90.58 ± 7.06 and 9.58 ± 2.39, respectively. With the elevating activity and expression of SphK1, the protein expressions of p38, p-p38 and SAPK/JNK were strikingly suppressed. On the contrary, after treating with DMS the protein expressions of p38, p-p38 and SAPK/JNK were enhanced.
  
  
  CONCLUSIONS
  SphK1 potently enhances the prolieration, migration and invasion of colon cancer HT-29 cells, meanwhile suppresses the cell apoptosis. The suppressing of the p38 and SAPK/JNK signalling pathways may be one of its molecular mechanisms.
authors.affiliation: Department of Gastroenterology, First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China.
authors.forename: Shi-quan
authors.initials: SQ
authors.lastname: Liu
authors.forename: Meng-bin
authors.initials: MB
authors.lastname: Qin
authors.forename: Jie-an
authors.initials: JA
authors.lastname: Huang
authors.forename: Yue-yuan
authors.initials: YY
authors.lastname: Zhong
authors.forename: Guo-du
authors.initials: GD
authors.lastname: Tang
authors.forename: Hai-xing
authors.initials: HX
authors.lastname: Jiang
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002273:Carcinogens / Q000008:administration & dosage / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D019073:HT29 Cells; D006801:Humans; D048670:MAP Kinase Kinase 4 / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D010766:Phosphorylation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism* / Q000502:physiology; D013110:Sphingosine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*; D000099157:Sphingosine Kinase
chemical_list: D002273:Carcinogens; D004791:Enzyme Inhibitors; D048670:MAP Kinase Kinase 4; D017853:Phosphotransferases (Alcohol Group Acceptor); D013110:Sphingosine; D013755:Tetradecanoylphorbol Acetate; D048051:p38 Mitogen-Activated Protein Kinases; D000099157:Sphingosine Kinase; C016658:phorbolol myristate acetate; C061800:N,N-dimethylsphingosine