Wen Jinhua, Matsumoto Kunio, Taniura Naoko, Tomioka Daisaku, Nakamura Toshikazu
Division of Molecular Regenerative Medicine, Department of Biochemistry and Molecular Biology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
Biochem Biophys Res Commun. 2007 Jun 22;358(1):117-23. doi: 10.1016/j.bbrc.2007.04.098. Epub 2007 Apr 23.
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 hydrodynamics-based 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.
NK4最初被制备为肝细胞生长因子（HGF）的竞争性拮抗剂，是一种双功能分子，可作为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NK4基因的表达质粒施用于小鼠时，通过重复施用NK4基因可使血浆NK4蛋白水平反复升高。将小鼠皮下植入结肠癌细胞，并每周给予NK4质粒。NK4基因的重复递送和表达抑制了皮下肿瘤组织中结肠癌细胞的血管生成和侵袭性，这与原发性肿瘤生长的抑制有关。肿瘤植入后50天，癌细胞自然转移至肝脏，而NK4基因表达可有效抑制肝转移。NK4基因表达对HGF-Met受体途径和肿瘤血管生成的抑制对于抑制结肠癌的侵袭、生长和转移具有潜在的治疗价值。
