Abstract

It has been discovered that hepatocellular carcinoma (HCC) has high ability of migration and angiogenesis. This study aimed to explore the mechanism of HCC cell migration and angiogenesis. BEL-7402 cell line was used as HCC cell model for investigating the regulation of cell migration upon c-Src inhibitors (PP2 and SU6656) treatment. Western blot was used for detecting the expression of MT1-MMP and VEGF-C. The activity of MMP2 and MMP9 was monitored with gelatin zymography assay. BEL-7402 cell migration and invasion was detected by wound healing assay and Transwell. Immunoprecipitation was used for detecting the interaction among c-Src, pro-MT1-MMP, Furin and VEGF-C. Our results have show that the expression of MT1-MMP and VEGF-C were inhibited by PP2 and SU6656, in accordance with c-Src activity. Zymography assay demonstrated that the activity of MMP2 and MMP9 decreased upon PP2 or SU6656 treatment. The invasion and migration of BEL-7402 were inhibited. We also found that c-Src interacted with Furin in vivo. The interaction between Furin and its substrates pro-MT1-MMP、pro-VEGF-C decreased upon c-Src inhibitors treatment. These findings indicate that the activity of c-Src inhibition associated with cell invasion and migration decreased by down-regulating the interaction between Furin and its substrates (pro-MT1-MMP, pro-VEGF-C).

Key words: Hepatocellular carcinoma (HCC), Furin, c-Src inhibitor, MT1-MMP, VEGF-C, cell migration.