Dickkopf-1 silencing inhibits invasion and epithelial-mesenchymal transition in gastric carcinoma cells by down-regulating β-catenin / 中国病理生理杂志

ABSTRACT

AIM: To explore the expression of Dickkopf-1 (DKK1) in human gastric carcinoma cells, and the influences of DKK1 gene silencing on cell invasion.METHODS: The levels of DKK1 in the human gastric mucosa cell line GES-1 and gastric carcinoma cell lines MKN-45 and SGC-7901 were detected by real-time PCR and Western blot.DKK1 gene was silenced by RNA interference, which was verified by real-time PCR, Western blot and ELISA.The cell invasion ability was determined by Transwell assay, and the cell proliferation was inhibited by mitomycin C.The levels of E-cadherin, N-cadherin, vimentin and β-catenin were determined by real-time PCR and Western blot.RESULTS: The expression of DKK1 was significantly higher in MKN-45 cells and SGC-7901 cells than that in GES-1 cells, indicating that DKK1 expression was obviously increased in gastric carcinoma cells.After successful silencing of DKK1 gene in the MKN-45 cells and SGC-7901 cells, the cell invasion ability was markedly decreased in a time-dependent pattern with increased expression of E-cadherin and decreased expression of N-cadherin and vimentin, indicating that DKK1 silencing dramatically inhibited gastric carcinoma cell invasion and epithelial-mesenchymal transition (EMT).The introduction of exogenous recombinant DKK1 (rDKK1) demonstrated the promoting effect of DKK1 on gastric carcinoma cell invasion and EMT.In addition, the inhibitory effects of DKK1 silencing on gastric carcinoma cell invasion and EMT were fulfilled by down-regulating β-catenin.CONCLUSION: The expression of DKK1 is significantly increased in human gastric carcinoma cells.Silencing of DKK1 markedly inhibits gastric carcinoma cell invasion and EMT by down-regulating β-catenin.