A Study On Mechanisms Underlying Effects Of Resveratrol On Cell Migration And Invasion Ability Of Human Glioma U87Cells

Objective To evaluate the effects of resveratrol（Res）on cell migration andinvasion ability of human glioma cell1ine U87cells and its mechanisms.Methods Cell viability of glioma U87cells treated with Rev in variableconcentration for24h,48h and72h was detected by methyl thiazolyl tetrazolium(MTT) assay; the cells’ migration and invasion were evaluated by in vitro woundhealing assay and Matrigel–Transwell assay respectively; activity ofmatrix-metalloproteinase (MMP)-2and MMP-9was determined by gelatinezymography assay; western blotting was taken to detect the effects of Res onexpression of ERK1/2, p-ERK1/2, AKT-1, p-AKT, p65(a subunit of NF-kB) andMMP-2; immuocytochemistry and immunoreactivity score analysis wereperformed to determine the change of protein level and sub-cellular localizationof p65in Res-treated U87cell. Results As MTT assay showed, compared with the untreated control, viabilityof glioma U87cell was significantly decreased (p <0.05) when treated with Resat60,80, and100μM for24,48h and72h. Compared with control, cellmigration and invasion ability of U87cells treated with40μM Res for24h or48h were inhibited obviously (p <0.05). The mean width of wound inRes-treated groups is wider than that of control, indicating Res decreases themigration ability of U87cells in vitro. When cells were incubated with40μMRes for24h or48h, mean quantity of cells that invaded through the Matrigel isdecreased significantly, indicating Res has potential to inhibit the invasionability of U87cell in vitro. Gelatin zymography assay revealed lower activity ofMMP-2in U87cells treated with40μM Res (p <0.05). Western blottingconfirmed Res-induced inhibition of MMP-2expression. Results byimmuocytochemistry showed the translocation of p65from the cytoplasm to thenucleus was reduced after40μM Res treatment. In addition, SN50, a NF-kBinhibitor, decreased both the activity and expression of MMP-2in U87cells.Moreover, the western blotting results showed that Res decreased bothp-ERK1/2and p-AKT-1protein level in U87cells after incubation for24and48h.Conclusion The data presented in this study demonstrated the anti-migrationand invasion potential of Res in glioma U87cells. The underlying mechanismsmay involve inhibition of MMP-2expression and activity, which is due toRes-induced suppression on activity of ERK1/2and AKT-1and subsequentlyNF-kB.