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

Dan Li, Bin Zhang, and Chao Hu

Department of Radiology, the Second Xiangya Hospital, Central South University, Changsha 410083, China

Acta Biochim Biophys Sin 2017, 49: 581–587; doi: 10.1093/abbs/gmx046

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, ectopically overexpressed 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.

Oxaliplatin inhibits HCC cell proliferation and migration and induces apoptosis via GAS7C and N-WASP/FAK/F-actin

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