siRNA targeting VEGF inhibits hepatocellular carcinoma growth and tumor angiogenesis in vivo.

作者: Esther Raskopf , Annabelle Vogt , Tilman Sauerbruch , Volker Schmitz

DOI: 10.1016/J.JHEP.2008.07.022

关键词: Cancer researchVascular endothelial growth factorVascular endothelial growth factor AAngiogenesisBiologyTube formationEx vivoEndothelial stem cellIn vivoCD31

摘要: Background/Aims We have investigated whether siRNA targeted against VEGF inhibits functional properties of endothelial cells in vitro and HCC tumor growth blood vessel formation vivo . Methods The influence siRNA-VEGF on cell proliferation, apoptosis tube were analyzed Antitumoral effects examined an orthotopic model after ex transfer or intraperitoneal treatment siRNA, respectively. Intratumoral microvessel density was assessed by CD31 staining. Results expression inhibited Hepa129 70% SVEC4-10 48% within two days transfection. In , proliferation reduced 23% 38%, Interference with signaling demonstrated pAKT hepatoma cells. Tumor application 83% 63% tumors 14 days. protein both models 29% 44%. Microvessel dropped to 34% for from transfected 39% systemic treated tumors. Conclusions results show that knockdown can be associated decreased

参考文章(31)
Deng-Fu Yao, Zhi-Zhen Dong, Li-Wei Qiu, Deng-Bing Yao, Xin-Hua Wu, Wei Wu, Yong Zhu, Gong-Sheng Shi, Xian-Yong Meng, Quantitative analysis of vascular endothelial growth factor, microvascular density and their clinicopathologic features in human hepatocellular carcinoma. Hepatobiliary & Pancreatic Diseases International. ,vol. 4, pp. 220- 226 ,(2005)
Goichi Matsumoto, Toshihiro Kushibiki, Yukihiko Kinoshita, Ushaku Lee, Yasushi Omi, Eiro Kubota, Yasuhiko Tabata, Cationized gelatin delivery of a plasmid DNA expressing small interference RNA for VEGF inhibits murine squamous cell carcinoma Cancer Science. ,vol. 97, pp. 313- 321 ,(2006) , 10.1111/J.1349-7006.2006.00174.X
Francesca Wannenes, Silvia Anna Ciafré, Francesco Niola, Gaetano Frajese, Maria Giulia Farace, Vector-based RNA interference against vascular endothelial growth factor-A significantly limits vascularization and growth of prostate cancer in vivo. Cancer Gene Therapy. ,vol. 12, pp. 926- 934 ,(2005) , 10.1038/SJ.CGT.7700862
V Schmitz, H Vilanueva, E Raskopf, T Hilbert, M Barajas, C Dzienisowicz, M Gorschlüter, J Strehl, C Rabe, T Sauerbruch, J Prieto, W H Caselmann, C Qian, Increased VEGF levels induced by anti-VEGF treatment are independent of tumor burden in colorectal carcinomas in mice Gene Therapy. ,vol. 13, pp. 1198- 1205 ,(2006) , 10.1038/SJ.GT.3302772
Hui Guan, Zhichao Zhou, Hua Wang, Shu-Fang Jia, Wenbiao Liu, Eugenie S. Kleinerman, A Small Interfering RNA Targeting Vascular Endothelial Growth Factor Inhibits Ewing's Sarcoma Growth in a Xenograft Mouse Model Clinical Cancer Research. ,vol. 11, pp. 2662- 2669 ,(2005) , 10.1158/1078-0432.CCR-04-1206
Ji Young Yoo, Joo-Hang Kim, Young-Guen Kwon, Eok-Cheon Kim, Nam Kyu Kim, Hye Jin Choi, Chae-Ok Yun, VEGF-specific Short Hairpin RNA–expressing Oncolytic Adenovirus Elicits Potent Inhibition of Angiogenesis and Tumor Growth Molecular Therapy. ,vol. 15, pp. 295- 302 ,(2007) , 10.1038/SJ.MT.6300023
Hui-Ling Shen, Wenlin Xu, Zhao-Yang Wu, Lei-Lei Zhou, Ru-Juan Qin, Hua-Rong Tang, Vector-based RNAi approach to isoform-specific downregulation of vascular endothelial growth factor (VEGF)165 expression in human leukemia cells. Leukemia Research. ,vol. 31, pp. 515- 521 ,(2007) , 10.1016/J.LEUKRES.2006.09.011
Adam Judge, Ian MacLachlan, Overcoming the Innate Immune Response to Small Interfering RNA Human Gene Therapy. ,vol. 19, pp. 111- 124 ,(2008) , 10.1089/HUM.2007.179
Rin Yamaguchi, Hirohisa Yano, Akihiro Iemura, Sachiko Ogasawara, Makoto Haramaki, Masamichi Kojiro, Expression of vascular endothelial growth factor in human hepatocellular carcinoma Hepatology. ,vol. 28, pp. 68- 77 ,(1998) , 10.1002/HEP.510280111