Up-regulation of SEPT7 Gene Inhibits Migration and Invasion of Human Glioma Cells in vitro and in vivo

The aim of this study was to explore the potential role of SEPT7 in glioma cell invasion. From in vitro experiments, we observed that the migratory and invasive abilities were inhibited in human glioblastoma U251MG and TJ899 cells after transfection with SEPT7 recombinant adenovirus constructs (Ad-SEPT7) as evaluated by Transwell assay, 3D Matrigel growth, 2D Matrigel growth and scratch assays. We further investigated the molecular events associated with the alteration of cell migration and invasion by immunohistochemistry and immuno uores-cence staining, Western blot and laser scanning confocal micros-copy analyses, and found the decreased expression of MMP2, MMP9, MT1-MMP and integrin αvβ3, increased expression of TIMP1 and TIMP2, and redistribution of intracellular cytoskel-eton tubulin-α. From in vivo study, it was demonstrated that the tumor growth rate in nude mice bearing xenograft subcutaneous U251 gliomas treated with Ad-SEPT7 was signi cantly slowed during the observation period of 4 weeks and the tumor volumes were much smaller than those in control and empty vector treated group. The expression of MMP2, MMP9, MT1-MMP and integrin αvβ3 was markedly inhibited while the expression of SEPT7, TIMP1, TIMP2 was upregulated in tumors treated with Ad-SEPT7. Taken together, these results suggest that SEPT7 plays an important role in glioma cell invasion and growth and it may be a candidate target for gene therapy of invasive gliomas.

The aim of this study was to explore the potential role of SEPT7 in glioma cell invasion. From in vitro experiments, we observed that the migratory and invasive abilities were inhibited in human glioblastoma U251MG and TJ899 cells after transfection with SEPT7 recombinant adenovirus constructs （AdSEPT7） as evaluated by Transwell assay, 3D Matrigel growth, 2D Matrigel growth and scratch assays. We further investigated the molecular events associated with the alteration of cell migration and invasion by immunohistochemistry and immunofluorescence staining, Western blot and laser scanning confocal microscopy analyses, and found the decreased expression of MMP2, MMP9, MT1-MMP and integrin ave3, increased expression of TIMP 1 and TIMP2, and redistribution of intracellular cytoskeleton tubuhn-a. From in vivo stud）5 it was demonstrated that the tumor growth rate in nude mice bearing xenograft subcutaneous U2S1 gliomas treated with Ad-SEPT7 was significantly slowed during the observation period of 4 weeks and the tumor volumes were much smaller than those in control and empty vector treated group.