Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, Republic of Korea.
J Nutr Biochem. 2011 Nov;22(11):1074-83. doi: 10.1016/j.jnutbio.2010.09.005. Epub 2011 Feb 2.
Hepatocyte growth factor (HGF) and c-Met have recently attracted a great deal of attention as prognostic indicators of patient outcome, and they are important in the control of tumor growth and invasion. Epigallocatechin-3-gallate (EGCG) has been shown to modulate multiple signal pathways in a manner that controls the unwanted proliferation and invasion of cells, thereby imparting cancer chemopreventive and therapeutic effects. In this study, we investigated the effects of EGCG in inhibiting HGF-induced tumor growth and invasion of oral cancer in vitro and in vivo. We examined the effects of EGCG on HGF-induced cell proliferation, migration, invasion, induction of apoptosis and modulation of HGF/c-Met signaling pathway in the KB oral cancer cell line. We investigated the antitumor effect and inhibition of c-Met expression by EGCG in a syngeneic mouse model (C3H/HeJ mice, SCC VII/SF cell line). HGF promoted cell proliferation, migration, invasion and induction of MMP (matrix metalloproteinase)-2 and MMP-9 in KB cells. EGCG significantly inhibited HGF-induced phosphorylation of Met and cell growth, invasion and expression of MMP-2 and MMP-9. EGCG blocked HGF-induced phosphorylation of c-Met and that of the downstream kinases AKT and ERK, and inhibition of p-AKT and p-ERK by EGCG was associated with marked increases in the phosphorylation of p38, JNK, cleaved caspase-3 and poly-ADP-ribose polymerase. In C3H/HeJ syngeneic mice, as an in vivo model, tumor growth was suppressed and apoptosis was increased by EGCG. Our results suggest that EGCG may be a potential therapeutic agent to inhibit HGF-induced tumor growth and invasion in oral cancer.
肝细胞生长因子（HGF）和 c-Met 最近作为患者预后的指标引起了极大的关注，它们在控制肿瘤生长和侵袭方面非常重要。表没食子儿茶素没食子酸酯（EGCG）已被证明能够以控制细胞不受控制的增殖和侵袭的方式调节多种信号通路，从而赋予癌症化学预防和治疗效果。在这项研究中，我们研究了 EGCG 抑制口腔癌细胞体外和体内 HGF 诱导的肿瘤生长和侵袭的作用。我们检查了 EGCG 对 HGF 诱导的 KB 口腔癌细胞系增殖、迁移、侵袭、凋亡诱导和 HGF/c-Met 信号通路调节的影响。我们在同种异体小鼠模型（C3H/HeJ 小鼠，SCC VII/SF 细胞系）中研究了 EGCG 的抗肿瘤作用和对 c-Met 表达的抑制作用。HGF 促进了 KB 细胞的增殖、迁移、侵袭和 MMP（基质金属蛋白酶）-2 和 MMP-9 的诱导。EGCG 显著抑制了 HGF 诱导的 Met 和细胞生长、侵袭以及 MMP-2 和 MMP-9 的表达的磷酸化。EGCG 阻断了 HGF 诱导的 c-Met 及其下游激酶 AKT 和 ERK 的磷酸化，EGCG 对 p-AKT 和 p-ERK 的抑制与 p38、JNK、cleaved caspase-3 和多聚 ADP-核糖聚合酶的磷酸化显著增加有关。在 C3H/HeJ 同种异体小鼠中，作为体内模型，EGCG 抑制了肿瘤生长并增加了凋亡。我们的结果表明，EGCG 可能是一种潜在的治疗剂，可抑制口腔癌中 HGF 诱导的肿瘤生长和侵袭。
