Combination gene therapy using VEGF-shRNA and fusion suicide gene yCDglyTK inhibits gastric carcinoma growth

Combination gene therapy using VEGF-shRNA and fusion suicide gene yCDglyTK inhibits gastric carcinoma growth
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DOI:
10.1016/j.yexmp.2011.07.007
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发表时间:
2011-12-01
影响因子:
3.6
通讯作者:
Leng, Aimin
Leng, Aimin
中科院分区:
医学3区
文献类型:
--
作者:
Liu, Ting;Ye, Ling;Leng, Aimin

文献摘要

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自杀基因疗法的临床试验只取得了有限的成功,这表明需要改进。血管生成在肿瘤的发展过程中起着至关重要的作用,而血管内皮生长因子在很大程度上调控着肿瘤的发展。本研究旨在评价血管内皮生长因子siRNA联合融合自杀基因yCDlyTK的抗肿瘤作用。在CDTK/5-FC系统中引入针对血管内皮生长因子的小发夹RNA(ShVEGF)可以更有效地诱导细胞凋亡,减少移植瘤组织中的微血管密度,从而显著延缓SGC7901移植瘤的生长。这些发现首次表明了使用自杀基因治疗和抗血管生成基因治疗相结合的基因治疗的潜力。(C)2011 Elsevier Inc.保留所有权利。
Clinical trials of suicide gene therapy have achieved limited success, which suggests a need for improvement. Angiogenesis plays a crucial role in the progression of cancers, which is greatly regulated by vascular endothelial growth factor (VEGF). The current study was designed to evaluate the anti-tumor effects of VEGF siRNA in combination with fusion suicide gene yCDglyTK. Introduction of a VEGF-targeted small hairpin RNA (shVEGF) to CDTK/5-FC system could induce cell apoptosis more effectively and decrease micro vessel density in xenograft tissue, thus resulted in a significant tumor growth delay in SGC7901 xenografts. These findings for the first time suggest the potential of combination gene therapy using suicide gene therapy and anti-angiogenesis gene therapy. (C) 2011 Elsevier Inc. All rights reserved.