siRNA targeting VEGF inhibits hepatocellular carcinoma growth and tumor angiogenesis in vivo
siRNA targeting VEGF inhibits hepatocellular carcinoma growth and tumor angiogenesis in vivo
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DOI：
10.1016/j.jhep.2008.07.022
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发表时间：
2008-12-01
影响因子：
25.7
通讯作者：
Schrnitz, Volker
中科院分区：
文献类型：
--
作者：
Raskopf, Esther;Vogt, Annabelle;Schrnitz, Volker
背景/目标：我们研究了靶向VEGF的siRNA是否抑制体外内皮细胞的功能特性和体内HCC肿瘤的生长和血管形成。方法：体外分析siRNA VEGF对内皮细胞增殖、凋亡和管形成的影响。分别在离体转移或腹膜内处理siRNA后，在原位肿瘤模型中检查抗肿瘤作用。结果：转染后2 d内，Hepa 129细胞VEGF表达抑制70%，SVEC 4 -10细胞VEGF表达抑制48%。在体外，内皮细胞增殖和管形成分别减少23%和38%。肝癌细胞中pAKT的降低证明了VEGF信号的干扰。在原位肿瘤中，通过离体转移或腹腔内应用siRNA-VEGF在14天内抑制肿瘤生长83%或63%。VEGF蛋白在两种模型中均降低了29%和44%。微血管密度下降到34%的肿瘤从体外转染细胞和39%的全身治疗tumors.Conclusions：结果表明，VEGF敲低可以与减少内皮细胞增殖和管形成ill体外和肿瘤生长和微血管密度ill体内。(C)2008年欧洲肝脏研究协会。Elsevier B. V.出版，保留所有权利。
Background/Aims: We have investigated whether siRNA targeted against VEGF inhibits functional properties of endothelial cells ill vitro and HCC tumor growth and blood vessel formation ill vivo.Methods: The influence of siRNA-VEGF on endothelial cell proliferation, apoptosis and tube formation were analyzed ill vitro. Antitumoral effects were examined in an orthotopic tumor model after ex vivo transfer or intraperitoneal treatment of siRNA, respectively. Intratumoral microvessel density was assessed by CD31 staining.Results:VEGF expression was inhibited in Hepa129 by 70% and in SVEC4-10 by 48% within two days after transfection. hi vitro, endothelial cell proliferation and tube formation was reduced by 23% and 38%, respectively. Interference with VEGF signaling was demonstrated by reduced pAKT in hepatoma cells. Tumor growth was inhibited by ex vivo transfer or intraperitoneal application of siRNA-VEGF by 83% or 63% in orthotopic tumors within 14 days. VEGF protein was reduced in both models by 29%, and 44%. Microvessel density dropped to 34% for tumors from ex vivo transfected cells and 39% for systemic treated tumors.Conclusions: The results show that VEGF knockdown can be associated with reduced endothelial cell proliferation and tube formation ill vitro and decreased tumor growth and microvessel density ill vivo. (C) 2008 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.