Department of Biotechnology, Bioenergy Research Center, Chonnam National University, 300 Yongbong-Dong, Buk-Gu, Gwangju 500-757, South Korea.
Phytomedicine. 2012 Feb 15;19(3-4):284-92. doi: 10.1016/j.phymed.2011.08.069. Epub 2011 Oct 5.
Ginsenoside Rd is a protopanaxadiol-type ginsenoside found in ginseng and is the active ingredient in several Oriental herbal medicines. We investigated the effects of ginsenoside Rd on tumor invasion and metastasis in the human hepatocellular carcinoma HepG2 and its possible mechanism of action. HepG2 cells were treated with ginsenoside Rd at different concentrations. Scratch wound and Boyden chamber assays were used to determine the effects of ginsenoside Rd on the migration and invasiveness of HepG2 cells, respectively. The molecular mechanisms by which ginsenoside Rd inhibited the invasion and migration of HepG2 cells were investigated by RT-PCR, Western blotting, gelatin zymography, promoter assay, and treatment with inhibitors of MAPK signaling. Immunofluorescence analysis was conducted to evaluate the effect of ginsenoside Rd on focal adhesion formation in HepG2 cells. Treatment with ginsenoside Rd dose- and time-dependently inhibited the migration and invasion of HepG2 cells. It achieved this by reducing the expression of MMP-1, MMP-2, and MMP-7, by blocking MAPK signaling by inhibiting the phosphorylation of ERK and p38 MAPK, by inhibition of AP-1 activation, and by inducing focal adhesion formation and modulating vinculin localization and expression. Treatment of HepG2 cells with ginsenoside Rd significantly inhibited metastasis, most likely by blocking MMP activation and MAPK signaling pathways involved in cancer cell migration. These findings may be useful for the development of novel chemotherapeutic agents for the treatment of malignant cancers.
人参中的人参皂甙 Rd 是一种原人参二醇型皂甙，是几种东方草药的有效成分。我们研究了人参皂甙 Rd 对人肝癌 HepG2 细胞侵袭和转移的影响及其可能的作用机制。用不同浓度的人参皂甙 Rd 处理 HepG2 细胞。划痕实验和 Boyden 室分析分别用于确定人参皂甙 Rd 对 HepG2 细胞迁移和侵袭的影响。通过 RT-PCR、Western blotting、明胶酶谱分析、启动子测定以及 MAPK 信号转导抑制剂处理，研究了人参皂甙 Rd 抑制 HepG2 细胞侵袭和迁移的分子机制。免疫荧光分析用于评估人参皂甙 Rd 对 HepG2 细胞焦点黏附形成的影响。用人参皂甙 Rd 处理 HepG2 细胞，呈剂量和时间依赖性地抑制其迁移和侵袭。其作用机制可能是通过降低 MMP-1、MMP-2 和 MMP-7 的表达，通过抑制 ERK 和 p38 MAPK 的磷酸化来阻断 MAPK 信号转导，通过抑制 AP-1 激活，通过诱导焦点黏附形成并调节 vinculin 定位和表达来实现的。用人参皂甙 Rd 处理 HepG2 细胞可显著抑制转移，这很可能是通过阻断 MMP 激活和参与癌细胞迁移的 MAPK 信号通路来实现的。这些发现可能有助于开发用于治疗恶性癌症的新型化疗药物。
