Oxaliplatin inhibits proliferation and migration of human hepatocellular carcinoma cells via GAS7C and the N-WASP/FAK/F-actin pathway

摘要

The growth arrest-specific gene 7 (GAS7),a member of the growth-arrest-specific family,encodes three protein isoforms (GAS7A,GAS7B,and GAS7C) and plays a potential role in lung cancer as a tumor suppressor gene.In the present study,we found low endogenous expressions of GAS7C mRNA and protein in hepatocellular carcinoma (HCC) cell lines compared with normal liver cells,and that there was a distinct increase of GAS7C expression in HCC cells treated with oxaliplatin.CCK8,apoptosis,and Transwell migration assays showed that cell proliferation and motility of HepG2 and MHCC-97 H cells were inhibited by oxaliplatin,while apoptosis was increased.Interestingly,western blot analysis showed that treatment with oxaliplatin increased GAS7C and N-WASP protein levels and decreased the levels of proteins involved in the fibronectin/integrin/FAK pathway,such as FAK,in both HCC cell lines.In addition,ectopicallyoverexpressed GAS7C obviously inhibited cell proliferation and cell motility.Flow cytometry results showed that overexpression of GAS7C induced apoptosis of HepG2 and MHCC-97 H cells.We further confirmed the correlation between GAS7C and the N-WASP/FAK/F-actin pathway by q-PCR and western blot analysis of in GAS7C-overexpressing HepG2 and MHCC-97 H cells.Inhibition of GAS7C substantially reversed the anti-cancer effect of oxaliplatin and blocked the activity of the N-WASP/FAK/F-actin pathway.Taken together,our results showed that oxaliplatin inhibits HCC cell proliferation and migration ability by up-regulating GAS7C and activating the N-WASP/FAK/F-actin pathway.