中文摘要：

应用阳离子聚合物聚乙烯亚胺（polyethyleneimine,PEI）包裹靶向小鼠VEGFR2基因的siRNA分子,以研究其体外基因沉默作用及不同给药途径的肿瘤生长抑制作用。采用共聚焦显微镜观察荧光染料CY3标记的siRNA分子的细胞内定位,RT-PCR和Western blotting检测VEGFR2mRNA和蛋白表达水平基因沉默效果,建立裸鼠皮下肿瘤模型比较经瘤内和尾静脉给予siVEGFR2/PEI抑制肿瘤生长的作用。共聚焦显微镜观察证实PEI能成功转染siRNA分子进入细胞质,siVEGFR2/PEI转染的MS1细胞中VEGFR2mRNA和蛋白表达水平明显下降,沉默效率分别为28.2%和23.6%。瘤内给与siVEGFR2/PEI组裸鼠肿瘤体积[（189.429±17.562）mm^3]明显小于空白组[（365.844±20.713）mm^3]和PEI静脉给药组[（315.507±20.491）mm^3]。结果表明,PEI能有效介导siRNA分子转染进入细胞质并能特异性沉默靶基因的表达。未经组织靶向性修饰的PEI不具有肿瘤靶向作用,瘤内注射的抗肿瘤效应优于静脉给药途径,这为进一步研究PEI介导的siRNA分子体内基因沉默效应的机制和优化该给药系统临床治疗肿瘤应用奠定了基础。

英文摘要：

The aim of this paper is to report the study on gene silencing efficiency of siRNA targeted against mouse VEGFR2 （siVEGFR2） in vitro mediated by polyethyleneimine （PEI） and its anti-tumor effect in vivo.CY3-labeled siRNA was compounded into PEI and transfected into MS1 cells.Confocal microscopy was used to image the subcellular distribution of siRNA in MS1 cells.Semi-quantitative RT-PCR and Western blotting were used to evaluate VEGFR2 gene silencing induced by siVEGFR2/PEI complexes.A tumor-bearing nude mice model was established to compare the anti-tumor effect after delivered by local and systemic routes.siVEGFR2/PEI complex-transfected cells exhibited much fluorescence in cytoplasm with no evidence of nuclear accumulation.The expression levels of VEGFR2 mRNA and protein in PEI-transfected cells were significantly down-regulated compared with that in blank group,the silencing efficiency were 28.2% and 23.6% respectively.The tumor sizes in mice intratumorally injected with siVEGFR2/PEI complexes （189.429 ± 17.562 mm^3） were reduced definitely compared to that in mice injected with siVEGFR2/PEI complexes via vein route （315.507 ± 20.491 mm^3）,or to saline groups （365.844 ± 20.713 mm^3）.The study demonstrated that PEI could effectively transfect siRNA into cells and silence the VEGFR2 gene expression.Intratumoral delivery is more suitable for non-targeted modified PEI/siRNA complexes to inhibit the tumor growth in vivo.The present data lay a solid foundation to further study on the gene silencing mechanism for PEI-medicated RNAi and its anti-tumor efficiency in vivo.