Research and Development Center for Plant Medicine and Plant Drugs, Xiamen Overseas Chinese Subtropical , Plant Introduction Garden, Xiamen, PR China.
Planta Med. 2011 Mar;77(5):428-33. doi: 10.1055/s-0030-1250454. Epub 2010 Oct 26.
The intestinal metabolite of ginseng saponin, compound K (CK), has various chemopreventive and chemotherapeutic activities, including anti-tumor 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- κB p65 and a concomitant increase in cytosolic NF- κB p65, indicating that CK suppressed the activation of the NF- κB pathway. Meanwhile, our study showed that the inhibition of matrix metalloproteinase2/9 (MMP2/9) expression caused by CK treatment was associated with NF- κB p65 nuclear export. Taken together, our results not only revealed that NF- κB 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.
人参皂苷的肠道代谢产物，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）转移生长的功能机制尚不清楚。在这里，我们使用多种体外和体内模型报告说，CK 强烈减弱 HCC 细胞的集落形成、黏附和侵袭能力，并且显著抑制 HCC 自发性转移生长。在分子水平上，免疫荧光和 Western blot 分析证实，CK 处理抑制 HCC 转移生长导致核 NF-κB p65 的时间依赖性减少，同时胞质 NF-κB p65 增加，表明 CK 抑制 NF-κB 途径的激活。同时，我们的研究表明，CK 处理抑制基质金属蛋白酶 2/9（MMP2/9）的表达与 NF-κB p65 核输出有关。总之，我们的结果不仅揭示了 NF-κB p65 核输出和 MMP2/9 表达的减少与 CK 诱导的转移抑制有关，而且表明 CK 可能成为预防和治疗 HCC 的潜在细胞毒性药物。
