Ginsenoside Compound K Attenuates Metastatic Growth of Hepatocellular Carcinoma, which Is Associated with the Translocation of Nuclear Factor-κB p65 and Reduction of Matrix Metalloproteinase-2/9
Ginsenoside Compound K Attenuates Metastatic Growth of Hepatocellular Carcinoma, which Is Associated with the Translocation of Nuclear Factor-κB p65 and Reduction of Matrix Metalloproteinase-2/9
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DOI：
10.1055/s-0030-1250454
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发表时间：
2011-03-01
期刊：
影响因子：
2.7
通讯作者：
Song, Gang
中科院分区：
文献类型：
--
作者：
Ming, Yanlin;Chen, Zhongyan;Song, Gang
人参皂苷的肠道代谢物化合物K （CK）具有多种化学预防和化学治疗活性，包括抗肿瘤活性。然而，CK减轻肝细胞癌（HCC）转移性生长的功能机制尚不清楚。在这里，我们使用多个体外和体内模型，我们报道了CK在体外强烈减弱肝癌细胞的集落形成、粘附和侵袭，并在体内显著抑制自发性肝癌转移生长。在分子水平上，免疫荧光和Western blotting分析证实，CK处理对肝癌转移性生长的抑制导致细胞核NF-kappa B p65的时间依赖性降低，同时细胞质NF-kappa B p65的增加，表明CK抑制了NF-kappa B通路的激活。同时，我们的研究表明，CK处理对基质金属蛋白酶2/9 （matrix metalloproteinase2/9, MMP2/9）表达的抑制与NF-kappa B p65核输出有关。综上所述，我们的研究结果不仅揭示了NF-kappa B p65核输出和MMP2/9表达的降低与CK诱导的转移抑制有关，而且表明CK可能成为一种潜在的细胞毒性药物，用于预防和治疗HCC。
The intestinal metabolite of ginseng saponin, compound K (CK), has various chemopreventive and chemotherapeutic activities, including antitumor activity. However, the functional mechanisms through which CK attenuates metastatic growth in hepatocellular carcinoma (HCC) remain unclear. Here, using multiple in vitro and in vivo models, we reported that CK strongly attenuated colony formation, adhesion, and invasion of HCC cells in vitro and dramatically inhibited spontaneous HCC metastatic growth in vivo. At the molecular level, immunofluorescence and Western blotting analysis confirmed that inhibition of metastatic growth of HCC induced by CK treatment caused a time-dependent decrease in nuclear NF-kappa B p65 and a concomitant increase in cytosolic NF-kappa B p65, indicating that CK suppressed the activation of the NF-kappa B pathway. Meanwhile, our study showed that the inhibition of matrix metalloproteinase2/9 (MMP2/9) expression caused by CK treatment was associated with NF-kappa B p65 nuclear export. Taken together, our results not only revealed that NF-kappa B p65 nuclear export and the reduction of MMP2/9 expression were associated with the metastatic inhibition induced by CK, but also suggested that CK may become a potential cytotoxic drug in the prevention and treatment of HCC.