Isoquercitrin, ingredients in <i>Tetrastigma hemsleyanum</i> Diels et Gilg, inhibits hepatocyte growth factor/scatter factor-induced tumor cell migration and invasion

Aberrant activation of hepatocyte growth factor/scatter factor (HGF/SF) and its receptor, Met, is involved in the development and progression of many human cancers. In the screening assay of extracts from the root tuber of <i>Tetrastigma hemsleyanum</i> Diels et Gilg, isoquercitrin inhibited HGF/SF-Met signaling as indicated by its inhibitory activity on HGF/SF-induced cell scattering. Further analysis revealed that isoquercitrin specifically inhibited HGF/SF-induced tyrosine phosphorylation of Met. We also found that isoquercitrin decreased HGF-induced migration and invasion by parental or HGF/SF-transfected bladder carcinoma cell line NBT-II cells. Furthermore, isoquercitrin inhibited HGF/SF-induced epithelial mesenchymal transition <i>in vitro</i> and the invasion/metastasis of HGF/SF-transfected NBT-II cells <i>in vivo</i>. Our data suggest the possible use of isoquercitrin in human cancers associated with dysregulated HGF/SF-Met signaling.肝细胞生长因子/散射因子（hepatocyte growth factor/scatter factor, HGF/SF）及其受体Met的异常激活，参与多种人类癌症的发生与进展。在针对三叶崖爬藤（*Tetrastigma hemsleyanum* Diels et Gilg）块根提取物的筛选实验中，异槲皮苷（isoquercitrin）可抑制HGF/SF-Met信号通路，该作用可通过其对HGF/SF诱导的细胞散射的抑制活性得以证实。进一步分析显示，异槲皮苷可特异性抑制HGF/SF诱导的Met酪氨酸磷酸化。我们同时发现，异槲皮苷能够降低亲本膀胱癌细胞以及转染HGF/SF的膀胱癌细胞系NBT-II经HGF诱导的迁移与侵袭能力。此外，异槲皮苷可在体外（in vitro）抑制HGF/SF诱导的上皮间质转化，并在体内（in vivo）抑制转染HGF/SF的NBT-II细胞的侵袭与转移能力。本研究数据表明，异槲皮苷有望应用于HGF/SF-Met信号通路失调相关的人类癌症治疗。