摘要
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。
Objective To investigate the effect of growth differentiation factor 15（GDF15） downregulation on cell proliferation of human glioblastoma U87MG cells.Methods Human glioblastoma U87MG cells with stable GDF15 downregulation was used as shGDF15 group.U87MG cells with scramble knockdown was used as scramble group.Protein expression levels of GDF15 were determined by Western blot analysis.Growth curve and Brd U incorporation assays were used to observe cell proliferation.Protein expression levels of ERK1/2 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 GDF15 decrease DNA synthesis in S phage and cell proliferation of human glioblastoma U87MG cells through inhibiting ERK pathway.GDF15 is a potential target of chemotherapy sensitivity in glioblastoma clinical treatment.
出处
《基础医学与临床》
CSCD
2017年第11期1557-1561,共5页
Basic and Clinical Medicine
基金
河南省基础与前沿技术研究计划(152300410162)
河南省科技攻关计划(172102310103)
