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  • Title: Lentivirus-mediated siRNA targeting VEGF inhibits gastric cancer growth in vivo.
    Author: Sun P, Yu H, Zhang WQ, Hu M, Lv R.
    Journal: Oncol Rep; 2012 Nov; 28(5):1687-92. PubMed ID: 22895814.
    Abstract:
    Vascular endothelial growth factor (VEGF), a crucial promoter of blood vessel growth, not only stimulates endothelial cell proliferation, migration and survival, but also increases vascular permeability. The promotion of angiogenesis is a well-known prerequisite for tumor growth, invasion and metastasis. Evidence has shown that VEGF is overexpressed in many types of tumor tissues. Small interfering RNA (siRNA) targeting VEGF may effectively suppress cell proliferation and induce apoptosis in tumor cells. In this study, we aimed to evaluate whether lentivirus-mediated siRNA targeting VEGF inhibits gastric cancer growth in vivo. The transfection of VEGF siRNA into SGC7901 human gastric cancer cells downregulated the expression of VEGF and Bcl-2, but upregulated the expression of p21. In a nude mouse model of subcutaneous xenografts, 24 days after VEGF siRNA treatment, the tumor volume and weight were significantly smaller in the VEGF siRNA group compared to the control scrambled siRNA group. Furthermore, the expression of VEGF, sirtuin 1 (SIRT1), survivin and Bcl-2 was downregulated, whereas the expression of p53 and p21 was upregulated in the tumor cells, indicating that VEGF siRNA induced apoptosis in gastric cancer cells by inhibiting SIRT1 expression, leading to p53 transcriptional upregulation and the activation of downstream p21, while suppressing Bcl-2 and survivin expression. Our results demonstrate that lentivirus-mediated siRNA targeting VEGF offers a potential strategy to prevent the growth of gastric cancer.
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