Abstract: 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 BrdU 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 could rescue the increased cell proliferation with GDF15 downregulation. Conclusion GDF15 decrease DNA synthesis in S phage and cell proliferation of human glioblastoma U87MG cells through inhibiting ERK pathway. And GDF15 might be a potential target of chemotherapy sensitivity in glioblastoma clinical treatment.

Key words: glioblastoma, GDF15, chemotherapy resistance, cell cycle