title: Antiproliferative effects of γ-secretase inhibitor, a Notch signalling inhibitor, in multiple myeloma cells and its molecular mechanism of action.
abstract: OBJECTIVE
  To investigate the effects of γ-secretase inhibitor (GSI), a Notch signalling inhibitor, on the proliferation of multiple myeloma cells in vitro and its molecular mechanism of action.
  
  
  METHODS
  RPMI 8226 cells were treated with increasing concentrations of GSI (0-20 µmol/l) for 24-72 h. Proliferation was measured using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) assay. Cell-cycle analysis was performed on RPMI 8226 cells treated with 0-10 µmol/l GSI for 48 h using flow cytometry. Expression of Notch signalling proteins (Notch1, Jagged 1 and Jagged 2), Bcl-2 and phosphorylated Akt (p-Akt) was determined using Western blotting in RPMI 8226 cells treated with various concentrations of GSI for various time periods.
  
  
  RESULTS
  GSI inhibited proliferation of RPMI 8226 cells in a concentration- and time-dependent manner by inducing G0/G1 cell-cycle arrest. GSI-mediated antiproliferative effects were associated with significant reductions in the expression of Notch1, Jagged1, Jagged2, p-Akt and Bcl-2.
  
  
  CONCLUSIONS
  Inhibition of the Notch signalling pathway by GSI may be a promising therapeutic approach for the treatment of multiple myeloma.
authors.affiliation: Department of Haematology, First Hospital of Quanzhou Affiliated to Fujian Medical University, Quanzhou, China.
authors.forename: Jiasheng
authors.initials: J
authors.lastname: Hu
authors.forename: Xiongpeng
authors.initials: X
authors.lastname: Zhu
authors.forename: Quanyi
authors.initials: Q
authors.lastname: Lu
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002135:Calcium-Binding Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005562:Formazans; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D000072100:Jagged-1 Protein; D000072101:Jagged-2 Protein; D008565:Membrane Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D011480:Protease Inhibitors / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D051881:Receptor, Notch1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D000072099:Serrate-Jagged Proteins; D013778:Tetrazolium Salts
chemical_list: D000970:Antineoplastic Agents; D002135:Calcium-Binding Proteins; D005562:Formazans; D036341:Intercellular Signaling Peptides and Proteins; C000606273:JAG1 protein, human; C490504:JAG2 protein, human; D000072100:Jagged-1 Protein; D000072101:Jagged-2 Protein; D008565:Membrane Proteins; C497761:NOTCH1 protein, human; D011480:Protease Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D051881:Receptor, Notch1; D000072099:Serrate-Jagged Proteins; D013778:Tetrazolium Salts; C079782:MTT formazan; D051057:Proto-Oncogene Proteins c-akt; D053829:Amyloid Precursor Protein Secretases
keywords: Multiple myeloma; Notch signalling pathway; phosphoinositide 3-kinase/Akt pathway; proliferation; γ-secretase inhibitor