OBJECTIVE: In this study, we investigated the effects of simvastatin on proliferation, migration, and apoptosis in human U251 and U87 glioma cells and the underlying molecular mechanism. METHODS: We used colony formation assay to test the cell proliferation, in vitro scratch assay to examine the cell migration, and caspase-3 activity assay, annexin V staining, and cytochrome C release to evaluate the cell apoptosis. Lipid raft fractions were isolated from glioma cells. Total cholesterol content assay was used to test the change of cholesterol level in lipid raft fractions. Immunocytochemistry staining was performed to detect the changes of lipid rafts in cell membranes. Western blotting analysis was performed to examine the signal transduction both in cells and in lipid raft fractions. RESULTS: Simvastatin inhibited proliferation and migration of U251 and U87 cells dose dependently. Simvastatin induced an increase of caspase-3 activity and annexin V staining, and down-regulated the phosphatidylinositol 3-kinase (PI3K)/Akt pathway. Simvastatin also decreased cholesterol content in lipid raft fractions, suppressed caveolin-1 expression in the lipid rafts, and induced Fas translocation into lipid rafts, suggesting that simvastatin may inhibit the prosurvival PI3K/Akt pathway and trigger caspase-3-dependent apoptotic cell death through the modulation of lipid rafts. CONCLUSION: These results suggest that modulation of lipid rafts, Fas translocation, and PI3K/Akt/caspase-3 pathway are involved in the antitumor effect of simvastatin and may have a potential role in cancer prevention and treatment.
OBJECTIVE: In this study, we investigated the effects of simvastatin on proliferation, migration, and apoptosis in human U251 and U87glioma cells and the underlying molecular mechanism. METHODS: We used colony formation assay to test the cell proliferation, in vitro scratch assay to examine the cell migration, and caspase-3 activity assay, annexin V staining, and cytochrome C release to evaluate the cell apoptosis. Lipid raft fractions were isolated from glioma cells. Total cholesterol content assay was used to test the change of cholesterol level in lipid raft fractions. Immunocytochemistry staining was performed to detect the changes of lipid rafts in cell membranes. Western blotting analysis was performed to examine the signal transduction both in cells and in lipid raft fractions. RESULTS:Simvastatin inhibited proliferation and migration of U251 and U87 cells dose dependently. Simvastatin induced an increase of caspase-3 activity and annexin V staining, and down-regulated the phosphatidylinositol 3-kinase (PI3K)/Akt pathway. Simvastatin also decreased cholesterol content in lipid raft fractions, suppressed caveolin-1 expression in the lipid rafts, and induced Fas translocation into lipid rafts, suggesting that simvastatin may inhibit the prosurvival PI3K/Akt pathway and trigger caspase-3-dependent apoptotic cell death through the modulation of lipid rafts. CONCLUSION: These results suggest that modulation of lipid rafts, Fas translocation, and PI3K/Akt/caspase-3 pathway are involved in the antitumor effect of simvastatin and may have a potential role in cancer prevention and treatment.
Authors: Daniel G Sedding; Jennifer Hermsen; Ulrike Seay; Oliver Eickelberg; Wolfgang Kummer; Carsten Schwencke; Ruth H Strasser; Harald Tillmanns; Ruediger C Braun-Dullaeus Journal: Circ Res Date: 2005-02-24 Impact factor: 17.367
Authors: J R Downs; M Clearfield; S Weis; E Whitney; D R Shapiro; P A Beere; A Langendorfer; E A Stein; W Kruyer; A M Gotto Journal: JAMA Date: 1998-05-27 Impact factor: 56.272
Authors: Caroline Happold; Thierry Gorlia; L Burt Nabors; Sara C Erridge; David A Reardon; Christine Hicking; Martin Picard; Roger Stupp; Michael Weller Journal: J Neurooncol Date: 2018-02-08 Impact factor: 4.130
Authors: Cari M Kitahara; Amy Berrington de González; Neal D Freedman; Rachel Huxley; Yejin Mok; Sun Ha Jee; Jonathan M Samet Journal: J Clin Oncol Date: 2011-03-21 Impact factor: 44.544
Authors: Zahid M Delwar; Dimitrios Avramidis; Elna Follin; Yan Hua; Åke Siden; Mabel Cruz; Kajsa M Paulsson; Juan Sebastian Yakisich Journal: Invest New Drugs Date: 2011-05-10 Impact factor: 3.850
Authors: David J Cote; Bernard A Rosner; Stephanie A Smith-Warner; Kathleen M Egan; Meir J Stampfer Journal: Eur J Epidemiol Date: 2019-09-26 Impact factor: 8.082