中文摘要：

目的：探讨利用 siRNA和靶向 G3BP的多肽药物下调 G3BP后对多种肿瘤细胞迁移能力的影响。方法采用人纤维肉瘤 HT1080细胞、乳腺癌 MCF-7细胞以及人非小细胞肺癌 H1299细胞，应用 siRNA特异性干扰 G3BP后，通过划痕实验观察其对肿瘤细胞迁移能力的影响；用多肽药物 GAP161作用于肿瘤细胞后，利用划痕实验以及 Transwell迁移实验观察其对肿瘤细胞迁移能力的影响；在 MCF-7细胞中高表达 G3BP1，在 MDA-MB-231细胞中用 siRNA下调 G3BP1后，采用人全基因芯片分析 G3BP1高表达和低表达后的基因表达谱，并进行信号通路分析。结果 siRNA特异性下敲 G3BP1和 G3BP2后，HT1080、MCF-7和 H1299细胞的迁移能力显著降低。利用靶向 G3BP的特异性多肽药物 GAP161作用于多种肿瘤细胞后，肿瘤细胞的迁移能力显著下调。全基因组芯片分析表明：多个基因同时在 G3BP1高表达和低表达组中发生变化，该变化与细胞迁移相关的细胞黏附、整合素、MAPK 等信号通路有关。结论 G3BP下调后能够显著降低肿瘤细胞的迁移能力。靶向 G3BP的多肽药物具有显著抑制肿瘤细胞迁移的作用。下调或者高表达 G3BP后可通过下调或者上调多种与细胞黏附、整合素、MAPK 等信号通路相关基因发挥作用。

英文摘要：

Objective To investigate the effect of G3BP down-regulation by siRNA or G3BP-targeted peptide GAP161 on tumor cell migration. Methods Effect of G3BP knockdown on tumor cell migration was examined by wound healing assay in HT1080, MCF-7 and H1299 cells. Effect of GAP161 on the migration of tumor cells was measured by wound healing assay and Transwell assay. Human whole genome oligonucleotide microarray was used to analyze the gene expression profiles in MCF-7 cells with G3BP1 over-expression and MDA-MB-231 cells with G3BP1 knockdown. Pathway analysis was then performed according to the microarray data. Results Down-regulation of G3BP1 and G3BP2 by specific siRNAs significantly inhibited cell migration in HT1080, MCF-7 and H1299 cells. GAP161 also significantly reduced the tumor cell migration ability. Whole genome microarray analysis showed that over-expression of G3BP1 and knockdown G3BP1 in MCF-7 and MDA-MB-231 cells, respectively, affected cell adhesion, integrin and MAPK signaling pathways in an opposite manner. Conclusion Knockdown of G3BP by siRNA significantly inhibited tumor cell migration. G3BP-targeted peptide G3BP1 markedly reduced the cell migration abilities. Over expression of G3BP1 could up-regulate genes expression associated with cell adhesion, integrin and MAPK signaling pathways, while down-regulation of G3BP1 exerts opposite effects.