Linus Pauling Institute, Oregon State University, Corvallis, OR 97331-6512, USA.
Arch Biochem Biophys. 2010 Sep 1;501(1):52-7. doi: 10.1016/j.abb.2010.03.017. Epub 2010 Mar 31.
The Met receptor tyrosine kinase is deregulated in a variety of cancers and is correlated with advanced stage and poor prognosis. Thus, Met has been identified as an attractive candidate for targeted therapy. We compared the tea polyphenol (-)-epigallocatechin-3-gallate (EGCG) and a specific Met inhibitor, SU11274, as suppressing agents of Met signaling in HCT116 human colon cancer cells. Treatment with hepatocyte growth factor increased phospho-Met levels, and this was inhibited in a concentration-dependent manner by EGCG and SU11274 (IC(50) 3.0 vs. 0.05muM, respectively). Downstream activation of Erk and Akt signaling pathways also was suppressed. Both compounds at a concentration of 5muM lowered cell viability and proliferation, with EGCG being more effective than SU11274, and the invasion of colon cancer cells in Matrigel assays was strongly inhibited. These findings are discussed in the context of the pleiotropic effects of tea catechins, their tissue metabolite levels, and the potential to inhibit colon cancer metastasis and invasion.
间质表皮转化因子（Met）受体酪氨酸激酶在多种癌症中失调，与晚期和预后不良相关。因此，Met 已被确定为靶向治疗的有吸引力的候选物。我们比较了茶多酚（-）-表没食子儿茶素没食子酸酯（EGCG）和一种特定的 Met 抑制剂 SU11274，作为 HCT116 人结肠癌细胞中 Met 信号的抑制因子。肝细胞生长因子处理增加了磷酸化 Met 水平，这被 EGCG 和 SU11274 以浓度依赖的方式抑制（IC50 分别为 3.0 和 0.05μM）。下游的 Erk 和 Akt 信号通路的激活也被抑制。两种化合物在 5μM 的浓度下降低细胞活力和增殖，EGCG 比 SU11274 更有效，Matrigel 测定中结肠癌细胞的侵袭也被强烈抑制。这些发现与茶儿茶素的多效性作用、其组织代谢物水平以及抑制结肠癌转移和侵袭的潜力有关。
