Anti-metastatic Activity of Epigallocatechingallate in Human Uveal Melanoma Cells

• Main Authors: Chi-Wu Chang, 張集武
• Other Authors: 楊順發
• Format: Others
• Language: zh-TW
• Published: 2015
• Online Access: http://ndltd.ncl.edu.tw/handle/14955297848362536440

博士 === 中山醫學大學 === 醫學研究所 === 103 === Epigallocatechingallate (EGCG), the major polyphenol in green tea, has been shown to downregulate matrix metalloproteinase-2 (MMP-2) in many cancer cell types. However, the effect of EGCG on the migration and expression of MMP-2 of uveal melanoma cells has not been reported. We studied this effect and relevant signaling pathways in a human uveal melanoma cell line M17. MTT study revealed that EGCG did not affect the cell viability of M17 cells up to 100 μM. Wound-healing assay showed that EGCG significantly reduced the migration ability of cells in a dose-dependent manner from 20 to 100 μM. Gelatin zymography showed that secreted MMP-2 activity was inhibited dose-dependently by EGCG, whereas the MMP-2 expression at protein and mRNA levels were not affected as determined by Western blot and RT-PCR. EGCG significantly increased the expressions of MMP-2 endogenous inhibitors (TIMP-2 and RECK) in M17 cells. Western blot analysis of MAPK signal pathways showed that EGCG significantly decreased phosphorylated ERK1/2 levels, but not p38 and JNK levels, in melanoma cells. ERK1/2 inhibitors also reduced the migration and activity of MMP-2 in M17 cells. The present study suggested EGCG at nontoxic levels could inhibit migration of melanoma cells via downregulation of activities of secreted MMP-2 through the inhibition of the ERK1/2 phosphorylation. Therefore, EGCG may be a promising agent to be explored for the prevention of metastasis of uveal melanoma.