HMG-CoA reductase inhibitors reduce glioma invasion and migration induced by microglial MMP-2

Abstract

Objective To reveal the influences of atorvastatin on glioma intiltrative properties and pro-tumorigenic effects of microglia.Methods The CCK-8 assay was used to detect viabilities of glioma cells and microglia cells that incubated with atorvastatin at 10-10 to 10-5 mol/L for 24h.Microglia conditioned medium (MCM) was prepared through GCM activating microglia.Then,by using Transwell chambers in glioma invasion and migration assay,cell invasion and migration ability of U87 incubated with MCM was measured.Meanwhile,with the intervene of 10-5 mol/L atorvastatin in the process of microglia activation,cell invasion and migration ability of U87 was measured.Cell invasion and migration ability of U87 incubated with or without 10 mol/Latorvastatin was also measured.Gelatin mography assay was used to detect MMP-2 andMMP-9 expressions of U87 and microglia.Results 10-mol/L of atorvastatin had no effect on cell viabilities of U87 and microglia (P ＞ 0.05).After being incubated with MCM for 24 h,the invasion and migration cell number of U87 were increased as compared to the control (P ＜ 0.001).While incubating U87 with atorvastatin and MCM for 24 h,the invasion and migration cell number of U87 were significantly decreased as compared to the MCM group (P ＜ 0.001).Additionally,the invasion and migration cell number of U87 were slightly decreased as compared to the control after being incubated with atorvastatin alone for 24 h (P ＜ 0.05).Our Gelatin zymography assay further shows that the MMP-2protein level of U87 and GCM-induced microglia were decreased after being incubated with atorvastatin for 24,h (P ＜ 0.001).Conclusion Atorvastatin reduces glioma invasion and migration by attenuating microglial MMP-2 expression. Key words: Microglia; Glioma; Atorvastatin ; Matrix metalloproteinase 2