Vitamin K2 Inhibits the Growth of Hepatocellular Carcinoma via Decrease of Des-Gamma-Carboxy Prothrombin
Vitamin K2 Inhibits the Growth of Hepatocellular Carcinoma via Decrease of Des-Gamma-Carboxy Prothrombin
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DOI：
10.1159/000167022
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发表时间：
2009-01-01
期刊：
影响因子：
3.3
通讯作者：
Cui, Shu-Xiang
中科院分区：
文献类型：
--
作者：
Ma, Meng;Qu, Xian-Jun;Cui, Shu-Xiang
背景：脱-γ-羧基凝血酶原（DCP）是肝细胞癌（HCC）细胞在缺乏维生素K时产生的一种血清蛋白。血清和组织DCP表达被认为反映了HCC的生物学恶性潜能。因此，我们的目的是检查维生素K（2）对DCP产生以及肿瘤细胞生长和侵袭的功效。方法：采用3-[4，5-二甲基噻唑-2-基]-2，5-二苯基四氮唑溴化物法检测细胞生长和活力。维生素K（2）在荷肝癌细胞的裸鼠体内的疗效进行了检查。用24孔transwell小室检测肝癌细胞的运动能力和侵袭能力。用电化学发光免疫分析法测定培养上清和小鼠血清中DCP的水平。采用免疫印迹和免疫组化方法检测DCP在HCC中的表达。结果如下：维生素K（2）（2-40 μ M）显著降低PLC/PRF/5和HepG 2细胞上清液和荷肝癌裸鼠血清中DCP的产生水平。用Western blot分析法和免疫组化法检测了DCP对肝癌细胞的抑制作用。维生素K（2）能抑制肝癌细胞的生长，减少肿瘤细胞的侵袭和迁移。此外，在体内也观察到肝癌生长的抑制作用，并且敏感性与小鼠血清中DCP的降低良好相关。结论：维生素K2可能通过降低DCP抑制肝癌细胞的生长和侵袭。版权所有（C）2008 S. Karger AG，巴塞尔
Background: Des-gamma-carboxy prothrombin (DCP) is a serum protein produced by hepatocellular carcinoma (HCC) cells in the absence of vitamin K. Serum and tissue DCP expressions are thought to reflect the biological malignant potential of HCC. Hence, we aimed to examine the efficacy of vitamin K(2) on the production of DCP as well as tumor cell growth and invasion. Methods: Cell growth and viability were evaluated by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay. The in vivo efficacy of vitamin K(2) was examined in nude mice bearing HCC cells. A 24-well transwell chamber was used to evaluate the motility and invasive ability of HCC cells. Levels of DCP in supernatant of cultures and in serum of mice were measured using an electrochemiluminescence immunoassay method. Western blot and immunohistochemical analysis were employed to evaluate the expression of DCP in HCC. Results: Vitamin K(2) (2-40 mu M) significantly decreased the levels of DCP production in supernatant of PLC/PRF/5 and HepG2 cells and in serum of nude mice bearing HCC xenografts. The inhibition of DCP was also observed using the assays of Western blot analysis in HCC cultures and immunohistochemical analysis in HCC xenografts in mice. As a result of administration of vitamin K(2), the capacity of HCC growth was inhibited and the invasion and migration of tumor cells were decreased. Furthermore, the inhibitory effects of HCC growth were also observed in vivo and the sensitivity was well correlated with the decrease of DCP in the serum of mice. Conclusion: Vitamin K(2) might suppress the growth and invasion of HCC cells via decrease of DCP. Copyright (C) 2008 S. Karger AG, Basel