Inhibition of colon cancer growth and metastasis by NK4 gene repetitive delivery in mice
Inhibition of colon cancer growth and metastasis by NK4 gene repetitive delivery in mice
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DOI：
10.1016/j.bbrc.2007.04.098
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发表时间：
2007-06-22
影响因子：
3.1
通讯作者：
Nakamura, Toshikazu
中科院分区：
文献类型：
--
作者：
Wen, Jinhua;Matsumoto, Kunio;Nakamura, Toshikazu
NK 4最初作为肝细胞生长因子（HGF）的竞争性拮抗剂制备，是一种双功能分子，其充当HGF拮抗剂和血管生成抑制剂。当通过基于流体动力学的递送将NK 4基因的表达质粒施用到小鼠中时，通过重复施用NK 4基因实现血浆NK 4蛋白水平的重复增加。小鼠皮下植入结肠癌细胞，每周给予NK 4质粒。NK 4基因的重复递送和表达抑制结肠癌细胞在皮下肿瘤组织中的血管生成和侵袭性，这与抑制原发性肿瘤生长有关。在肿瘤植入后50天，癌细胞自然转移到肝脏，而NK 4基因表达有效地抑制了肝转移。通过NK 4基因表达抑制HGF-Met受体通路和肿瘤血管生成，对于抑制结肠癌的侵袭、生长和转移具有潜在的治疗价值。(c)2007年爱思唯尔公司All rights reserved.
NK4, originally prepared as a competitive antagonist for hepatocyte growth factor (HGF), is a bifunctional molecule that acts as an HGF-antagonist and angiogenesis inhibitor. When the expression plasmid for NK4 gene was administered into mice by hydrodynamicsbased delivery, the repetitive increase in the plasma NK4 protein level was achieved by repetitive administration of NK4 gene. Mice were subcutaneously implanted with colon cancer cells and weekly given with the NK4 plasmid. The repetitive delivery and expression of NK4 gene inhibited angiogenesis and invasiveness of colon cancer cells in subcutaneous tumor tissue and this was associated with suppression of primary tumor growth. By fifty days after tumor implantation, cancer cells naturally metastasized to the liver, whereas NK4 gene expression potently inhibited liver metastasis. Inhibition of the HGF-Met receptor pathway and tumor angiogenesis by NK4 gene expression has potential therapeutic value toward inhibition of invasion, growth, and metastasis of colon cancer. (c) 2007 Elsevier Inc. All rights reserved.