目的：从基因—蛋白—细胞效应多层次水平，观察Tiam-1反义基因下调肿瘤细胞内转移相关基因Tiam-1 mRNA和调节细胞骨架结构的Rho蛋白表达水平,探讨遏制肿瘤侵袭转移的作用和机制。方法： 采用反义核酸技术合成Tiam-1反义寡核苷酸，硫代化修饰与脂质体形成复合物（Tiam-1 ASODNS-Lf）,转导入人高转移巨细胞肺腺癌 PG细胞。采用 RT-PCR技术检测Tiam-1的表达水平，流式细胞术检测Rho蛋白表达水平，Matrigel体外转移模型检测PG细胞的侵袭转移力。结果： Tiam-1ASODNS-Lf抑制PG细胞Tiam-1 mRNA表达水平，其相对表达值从0.86下降为0.38；显著抑制PG细胞内Tiam-1介导的信号传递相关Rho蛋白表达水平，其表达率从27.96%降至16.86%(P<0.001)。显著抑制穿过人工基底膜的侵袭转移PG细胞数，从945±40下降为649±35(P<0.05)。结论：Tiam-1反义基因下调PG细胞中侵袭诱导基因mRNA表达及其介导的信号传递蛋白Rho的表达，从而遏制其侵袭和转移能力

Objective： Tiam-1 antisense gene was used to downregulate Tiam-1 mRNA and protein expression, thus tumor metastasis could be suppressed. Methods：In this study Tiam-1 mRNA was examined by RT-PCR. The expression of Rho protein was examined by flow cytometry. Basement membrane was used to examine the effect of Tiam 1 antisense gene on metastatic behavior of PG cells. Results：The relative expression level of Tiam-1 mRNA was reduced after exposure to Tiam-1 ASODNS-Lf. Only 72 hours of exposure to Tiam-1 ASODNS, cell metastasis of treated group was inhibitted significantly. The invasive cell numbers through matrigel reduced from 945±40 to 649±35 (P<005). Tiam-1 ASODNS-Lf significantly inhibitted Rho protein expression ratio from 27.86% to 16.86%(P<0.001), which related to signal transduction pathway. Conclusions：Antisense gene inhibits invasion and metastasis of tumor cells through a cascade reaction of gene-protein-cell effect and provides the theoretical and experimental bases for clinical therapy and study of antimetastasis.

山东省自然科学基金资助项目（Y99C06）