ABSTRACT
BACKGROUND AND OBJECTIVES: Aberrant activation of hepatocyte growth factor (HGF) and its receptor, c-Met, has been known to be involved in many human cancer development and progression. During the search for an effective molecule inhibitor of HGF/ c-Met signaling, we have found that Epigallocatechin-3-gallate (EGCG) in green tea might inhibit HGF/c-Met signaling. Studies were performed to address whether EGCG inhibited HGF-dependent tumor proliferation and invasion in HNSCC. MATERIALS AND METHOD: For EGCG inhibition of HGF/c-Met signaling, Western blot was performed. The proliferation of FaDu cells was assayed by counting the number of the cells after treatment by HGF 0, 10 ng/ml, EGCG 1 micrometer, EGCG 10 micrometer, HGF 10+EGCG 1 micrometer, HGF 10+EGCG 10 micrometer. The dispersion of cells was observed by measuring the separation and morphologic changes of the cells after treatment with HGF 0, 10 ng/ml HGF 10+EGCG 1 micrometer, HGF 10+EGCG 10 micrometer for 24 hours. Tumor cell migration was assessed by wound healing assay and tumor cell invasiveness was assessed by the membrane invasion assay. RESULTS: HGF treatment induced rapid activation of c-Met and EGCG inhibited HGF-induced c-Met signaling in FaDu cells. HGF significantly enhanced the growth of HNSCC cells and this phenomenon was inhibited by EGCG in a dose-dependant manner (p<0.05). EGCG inhibited HGF-induced scattering, migration, and invasion of HNSCC cells in a dose-dependent manner (p<0.05). CONCLUSION: Inhibition of HGF/Met by EGCG leads to decreased proliferation, scattering, migration and invasion in vitro, suggesting the possible use of EGCG in HNSCC associated with down-regulation of HGF/Met signaling.