GDF15表达下调促进人胶质母细胞瘤细胞系U87MG增殖

摘要

Objective To investigate the effect of growth differentiation factor 15 ( GDF15 ) downregulation on cell proliferation of human glioblastoma U 87MG cells.Methods Human glioblastoma U87MG cells with stable GDF15 downregulation was used as shGDF 15 group.U87MG cells with scramble knockdown was used as scramble group . Protein expression levels of GDF 15 were determined by Western blot analysis .Growth curve and BrdU incorporation assays were used to observe cell proliferation .Protein expression levels of ERK 1/2 and p-ERK1/2 were determined by western blot analysis .CCK-8 assays were used to observe cell proliferation .Results Compared with scramble cells, GDF15 downregulation significantly promoted cell proliferation ( P<0.05 ) , increased DNA synthesis in S phage ( P<0.01 ) , enhanced activity of ERK pathway and cell tolerance to VM-26 ( P<0.05 ) .Moreover , ERK pathway inhibitor rescued the increased cell proliferation with GDF15 downregulation.Conclusions GDF15decrease DNA synthesis in S phage and cell proliferation of human glioblastoma U 87MG cells through inhibiting ERK pathway .GDF15 is a potential target of chemotherapy sensitivity in glioblastoma clinical treatment .%目的 探讨生长分化因子15(GDF15)表达下调对人胶质母细胞瘤U87MG细胞系增殖的影响.方法选取稳定下调GDF15的人胶质母细胞瘤U87MG细胞作为shGDF15组,以scramble细胞作为对照组.Western blot检测GDF15蛋白表达;增殖曲线和BrdU掺入实验检测细胞增殖;Western blot检测ERK1/2和p-ERK1/2蛋白表达;CCK-8实验检测细胞增殖.结果与scramble组相比较,shGDF15组细胞增殖明显加快(P<0.05);细胞周期S期DNA合成增加(P<0.01);ERK通路激活水平明显增加(P<0.05);对化疗药物VM-26的耐受性明显增强(P<0.05),并且ERK通路抑制剂可降低GDF15表达下调促进细胞增殖作用.结论GDF15可通过下调ERK通路抑制人胶质母细胞瘤U87MG细胞S期DNA合成及细胞增殖,可作为提高胶质瘤临床化疗敏感性的潜在靶点.