基于HGF/c-Met信号通路探讨中药QHF复方抗肝癌转移作用及分子机制

Hepatocellular carcinoma (HCC) is easy to recurrence and metastasis that are most closely relationship with HGF/c-MET signaling pathway, and targeting this signaling cascade may affect carcinogenesis process. Our initial screening of the Chinese traditional medicine QHF formula significantly inhibit the proliferation and metastasis of liver cancer highly metastatic xenografts tumor in nude mice, down-regulated the expression of HGF and p-c-MET in liver cancer tissue. For this reason, this project seeks to further confirm QHF formula can significant against hepatocellular carcinoma invasion metastasis, and to explore the relationship between this role and the HGF/c-MET signaling pathway, to clarify its specific pathway and mechanisms. On the basis of using HGF cDNA and NK4 cDNA transfection of hepatoma cells and establish a nude mice model of liver cancer, combined stromal cells with metastatic potential of HCC cells in vitro cell culture, and using c-Met, PI3K, MAPK, Rac inhibitor for the corresponding parallel comparison, and detecting HGF/c-Met signaling pathway-related genes and protein expression and the ability of liver cancer cell invasion and metastasis. We will explore the QHF formula inhibit the expression of HGF and c-MET phosphorylation, activating PI3K, MAPK signaling cascades reaction, thereby affecting the molecular mechanisms of liver cancer metastasis, which will provide experimental evidence to look for an effective anti-liver metastasis drugs and therapeutic targets.

肝细胞癌（HCC）的高复发和高转移性，与HGF/cMet信号通路密切相关，靶向这一信号级联可影响癌变的进程。我们前期筛选得到的治疗肝癌中药有效成分验方QHF，能显著抑制裸鼠高转移性肝癌移植瘤的增殖与转移，下调瘤组织中HGF、p-cMet的表达。有鉴于此，本项目试图在确证QHF复方抗肝癌转移作用显著的基础上，进一步探讨该作用与HGF/cMet信号通路的关系，阐明其具体作用途经和机制。拟用HGF cDNA和NK4 cDNA转染肝癌细胞并建立裸鼠肝癌模型，结合间质细胞、转移潜能肝癌细胞体外培养，以c-Met、PI3K、MAPK和Rac抑制剂作对应级联平行对照，检测其HGF/c-Met信号通路的相关基因和蛋白的表达及肝癌细胞侵袭转移能力，探讨QHF复方抑制其HGF表达及cMet磷酸化，阻断PI3K、MAPK等级联反应，进而影响肝癌转移的分子机制，为寻找有效的抗肝癌转移药物和治疗靶点提供实验依据。

肝细胞癌（HCC）的高复发和高转移性，与HGF/cMet信号通路密切相关，靶向这一信号级联可影响癌变的进程。我们前期筛选得到的治疗肝癌中药有效成分验方QHF，能显著 抑制裸鼠高转移性肝癌移植瘤的增殖与转移，下调瘤组织中HGF、p-cMet的表达。有鉴于此，本项目在确证QHF复方抗肝癌转移作用显著的基础上，进一步探讨该作用与HGF/c Met信号通路的关系，阐明其具体作用途经和机制。用HGF cDNA和NK4 cDNA转染肝癌细胞并建立裸鼠肝癌模型，结合间质细胞、转移潜能肝癌细胞体外培养，以c-Met、PI3K、MAPK和Rac抑制剂作对应级联平行对照，检测其HGF/c-Met信号通路的相关基因和蛋白的表达及肝癌细胞侵袭转移能力，探讨QHF复方抑制其HGF表达及cMet磷酸化，阻断PI3K、MAPK 等级联反应，进而影响肝癌转移的分子机制，为寻找有效的抗肝癌转移药物和治疗靶点提供实验依据。