中文摘要：

目的研究隔蛋白7（SEPT7）基因对人胶质瘤细胞系TJ899侵袭的抑制及其分子机制。方法Transwell法和3-D Matrigel法、划痕实验和2-D Matrigel法观察转染SEPT7的TJ899胶质瘤细胞侵袭、迁移能力变化，蛋白印记和免疫组织化学检测MMP2、MMP9、MT1-MMP、TIMP1和TIMP2的表达变化，蛋白印记和免疫荧光检测整合素αV β3的表达，应用激光扫描共聚焦显微镜观察细胞骨架蛋白tubulin-α结构的变化。结果Transwell法和3-D Matrigel法观察转染SEPT7后TJ899细胞的侵袭能力下降了59．86％、43．36％，划痕实验和2-D Matrigel法观察和迁移能力下降了65．45％、24．02％。转染SEPT7后，MMP2、MMP9、MT1-MMP和整合素αVβ3的表达分别下调了54．03％、39．13％、76．06％、53．09％，TIMP1和TIMP2的表达则上调了62．50％、77．78％。肿瘤细胞的微管蛋白Tubulin-α结构出现了重新分布，由高密度型变化为稀疏型，这种变化接近于正常的非肿瘤的细胞的微管蛋白Tubulin-α结构。结论SEPT7基因可以抑制胶质瘤细胞的侵袭和迁移能力，其分子机制可能通过逆转MMPs／TIMPs的失衡状态，降低整合素αVβ3的表达，以及改变细胞骨架tubulin-α的结构而实现的。SEPT7可作为胶质瘤基因治疗的重要候选基因。

英文摘要：

Objective To study the anti-invasion effect of SEPT7 gene on TJ899 glioma cells and its molecular mechanism. Methods Tumor invasion and migration were examined by Transwell method and 3 D-Matrigel assay,wound-healing method and 2 D-Matrigel assay after SEPT7 transfection to TJ899 ceils. Three major molecular events associated with the cell motility and migration, including the alteration of MMP2, MMPg, MT1-MMP, TIMP1 and TIMP2, the alteration of integrin αVβ3 expression, and the structural change of cytoskeleton protein, tubulin-α,in TJ899 cells transfected with rAdS-SEPT7 were studied by Western blot, immunohistochemistry, immunofluorescence and laser scanning confocal microscope, respectively. Results The invasive capabilities of ceils transfected with rAdS-SEPT7 were inhibited to 59.86% （detected by transwell） and 43.36% （detected by 3-D matrigel assay）. The migratory capabilities of ceils transfected with rAdS-SEPT7 were inhibited to 65.45% （ detected by wound-healing method） and 24.02% （ detected by 2-D matrigel assay）. The expression of extracellular matrix metalloproteinases MMP-2,MMP-9, MT1-MMP and integrin αVβ3 was significantly decreased to 54. 03%, 39. 13%, 76.06% ,53.09% ,while the expression of matrix metaUoproteinase inhibitor TIMP1 ,TIMP2 was up-regulated to 62.50% and 77.78% respectively. Intracellular cytoskeleton protein tubulin-α in TJ899 ceils transfected with rAdS-SEPT7 exhibited prominent morphological changes from high density to low density, and this feature of alteration was similar to the tubulin-α structure in normal non-tumor ceils. Conclusion SEPT7 gene can inhibit the invasion and migration ability of TJ899 glioma ceils. Its molecular mecha- nism may include that SEPT7 gene reverses the imbalance state of MMPs/TIMPs, down-regulates the expression of integrin αVβ3 and alters the structure of tubulin-α of TJ899 glioma ceils. It is suggested that SEPT7 gene could be used as a good candidate for gene therapy of gliomas.