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  • Title: Efficient inhibition of non-small-cell lung cancer xenograft by systemic delivery of plasmid-encoding short-hairpin RNA targeting VEGF.
    Author: Yang Y, Bai Y, Xie G, Zhang N, Ma YP, Chen LJ, Jiang Y, Zhao X, Wei YQ, Deng HX.
    Journal: Cancer Biother Radiopharm; 2010 Feb; 25(1):65-73. PubMed ID: 20187798.
    Abstract:
    Vascular endothelial growth factor (VEGF) plays an important role in the growth and metastasis of non-small-cell lung cancer (NSCLC). The aim of this study was to develop an RNA-interference approach that targets VEGF, using a recombinant plasmid, and to explore its antitumor efficacy in NSCLC in vivo. shRNA-targeting VEGF was cloned into pGenesil-2 plasmid vector and then transfected into A549 human lung cancer cells, using cationic liposome. Reverse-transcriptase polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) analysis were used to evaluate the silencing effects of VEGF-shRNA on A549 cells in vitro. Further, the growth-inhibition capacity of VEGF-shRNA on A549 lung carcinoma xenografts was tested in nude mice. Proliferation, apoptosis, and angiogenesis in tumor tissues were measured by PCNA, TUNEL, and CD31 immunohistochemistry, respectively. shRNA-targeting VEGF significantly silenced VEGF expression in A549 lung cancer cells, as confirmed by RT-PCR and ELISA assay (P < 0.01). In vivo, the VEGF-shRNA delayed tumor growth and reduced tumor weight by approximately 61.96%, compared with control groups (P < 0.05), accompanied with angiogenesis inhibition (P < 0.01) and apoptosis induction (P < 0.01). Our data showed that the knockdown of VEGF by shRNA might be a potential therapeutic approach against human NSCLC.
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