TGF-β Regulates Survivin to Affect Cell Cycle and the Expression of EGFR and MMP9 in Glioblastoma.

Transforming growth factor beta (TGF-β) is suggestive of a molecular target for cancer therapy due to its involvement in cell cycle, differentiation, and morphogenesis. Meanwhile, survivin is identified as an apoptosis inhibitor and involved in tumorgenesis. Here, we aimed to investigate the potential associations between TGF-β and survivin in glioblastoma U87 cell line. Survivin small interfering RNA (siRNA), Western blotting, and cell cycle analysis were introduced to detect relevant proteins in TGF-β pathways. In this study, we observed a concentration- and time-dependent increase of survivin expression after treatment with TGF-β1. However, the kinase inhibitors U0126 and LY294002 inhibited the upregulation of survivin in comparison with DMSO. In addition, survivin siRNA effectively abrogated survivin expression in U87 cells, therefore affected cells' entry into the S phase of cell cycle, and then repressed the expression of epidermal growth factor receptor (EGFR) and matrix metalloproteinase 9 (MMP9) in comparison with non-transfection. In conclusion, the present study shows that TGF-β upregulates survivin expression via ERK and PI3K/AKT pathway, leading to glioblastoma cell cycle progression. Thus, the blockade of survivin will allow for the treatment of glioblastoma, partially attributing to the inhibition of EGFR and MMP9 expression.