Silence of VEGFR2 expression mediated by PEI/siRNA complexes.
- Author:
Huan YANG
1
;
Ou CHE
;
Shan CHEN
;
Liang SUN
;
Ai-Min JI
Author Information
1. Center of New Drug R&D, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China.
- Publication Type:Journal Article
- MeSH:
Animals;
Cell Line, Tumor;
Cells, Cultured;
Endothelial Cells;
cytology;
metabolism;
Female;
Gene Silencing;
Humans;
Lung Neoplasms;
metabolism;
pathology;
Mice;
Mice, Nude;
Neoplasm Transplantation;
Polyethyleneimine;
chemistry;
RNA, Messenger;
metabolism;
RNA, Small Interfering;
genetics;
metabolism;
Spleen;
cytology;
Transfection;
Tumor Burden;
Vascular Endothelial Growth Factor Receptor-2;
genetics;
metabolism
- From:
Acta Pharmaceutica Sinica
2010;45(5):576-581
- CountryChina
- Language:Chinese
-
Abstract:
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 mm3) were reduced definitely compared to that in mice injected with siVEGFR2/PEI complexes via vein route (315.507 +/- 20.491 mm3), or to saline groups (365.844 +/- 20.713 mm3). 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.
