Role of c-Src inhibitor in the regulation of hepatocarcinoma cell migration

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.