Human sulfatase-1 inhibits the migration and proliferation of SMMC-7721 hepatocellular carcinoma cells by downregulating the growth factor signaling

摘要

Aim: The human sulfatase-1 (hSulf-1) gene regulates the sulfation of heparan sulfate proteoglycans (HSPG) and suppresses tumorigenesis and angiogenesis by inhibiting several growth factor signaling pathways. Because the serine-threonine protein kinase (AKT) and extracellular signal-regulated kinase (ERK) signaling pathways are critical in cell survival, proliferation, migration and angiogenesis, the possible correlation between hSulf-1 and AKT/ERK signaling in hepatocellular carcinoma (HCC) cells needs further exploration. Methods: Adenovirus Ad5-hSulf1 carrying the hSulf-1 gene, and vectors carrying hSulf-1 shRNA, AKT shRNA and ERK shRNA were constructed and used to manipulate the expression of hSulf-1, AKT and ERK in SMMC-7721 cells. The scarification test, transwell and 3-(4 5-dimethylthiazol-2-yl)-2 5-diphenyltetrazolium bromide assays were used to examine the cellular migration and proliferation, and the expression of hSulf-1 and signaling factors, including the total and phosphorylated AKT and ERK, was analyzed by western blot in SMMC-7721 cells. Results: After infection with Ad5-hSulf1, the expression of hSulf-1 was increased with viral multiplicity of infection in SMMC-7721 cells. Compared with the control adenovirus Ad5-EGFP and blank control groups, cells in the Ad5-hSulf1 group were showed that the phosphorylation of AKT and ERK was decreased. Meanwhile, the cell migration and cell viability were obviously suppressed. Conclusion: The expression of hSulf-1 mediated by adenovirus in HCC cells could downregulate the activity of AKT and ERK signaling pathways, and inhibit HCC cell migration and proliferation. The hSulf-1 gene may be considered as a candidate of antitumor factor for cancer gene therapy.