Effects of adenovirus-mediated VEGF-siRNA on the growth of xenografted human osteosarcoma in nude mice
- Author:
Guang QIAN
1
Author Information
1. Department of Othopeadics
- Publication Type:Journal Article
- Keywords:
Gene therapy;
Mice, nude;
Osteosarcoma;
RNA, small interfering;
Vascular endothelial growth factors
- From:
Tumor
2007;27(12):948-952
- CountryChina
- Language:Chinese
-
Abstract:
Objective: Tumor growth and metastasis depend on angiogenesis. VEGF is the key gene in angiogenesis. The angiogenesis could be inhibited by blockade of VEGF expression thus suppressing the growth and metastasis of tumor. This study aimed to design a short hairpin RNA targeting VEGF, construct its adenovirus eukaryotic expression vector (Ad-VEGF-siRNA), and observe the effects of Ad-VEGF-siRNA transfection on growth of xenografted osteosarcoma MG 63 in nude mice. Methods: The Ad-VEGF-siRNA was transfected into cultured human osteosarcoma cell line MG 63. In vitro cell growth activities were tested by MTT assay. The expression of VEGF was determined using RT-PCR method. The xenograft model of nude mice was established. The Ad-VEGF-siRNA was injected intotumor body regularly. The tumor formation rate, tumor volume, tumor inhibiting rate, and the expression of apoptosis and proliferation-related genes were measured. Results: Transfection of Ad-VEGF-siRNA significantly inhibited the growth of MG 63 cells. The weight and volume of xenografted osteosarcoma significantly decreased compared with the control group after intratumor injection of Ad-VEGF-siRNA (P < 0.01). TUNEL staining showed that the apoptosis of MG 63 cells increased. Immunohistochemistry suggested that the expression of bcl-2 significantly decreased in osteosarcoma tissues (P < 0.01). Conclusion: Ad-VEGF-siRNA specifically and efficiently blocked the expression of VEGF with high efficiency, significantly inhibited the growth of xenografted osteosarcoma in nude mice, and induced the apoptosis of osteosarcoma MG 63 cells.
