Effect of Sorafenib combined with 5-nitrogen impurity-2'-deoxy cytidine on the expression of DNMT3B gene in hepatocellular carcinoma SMMC-7721 cells

Objective:To study the effects of the sorafenib combined with 5-nitrogen impurity-2'-deoxy cytidine on human hepatocellular carcinoma SMMC-7721 cells,and investigate the possible molecular mechanism of regulating the DNMT3B gene expression.Methods:After separate and combined medication,the proliferation,invasion and apoptosis of SMMC-7721 cells were detected using MTT method,transwell method and flow cytometry,respectively.The protein expressions of DNMT3B,p-Akt -Ser473 and ERK were measured using Western blotting.Results:The IC50 of sorafenib and 5-nitrogen impurity-2'-deoxy cytidine to hepatocellular carcinoma SMMC-7721 cells were 11 μmol/L and 6 μmol/L respectively.The 6 μmol/L of sorafenib combined with 4 μmol/L of 5-nitrogen impurity-2'-deoxy cytidine was used as the subsequent drug concentration.Compared with the control group,the separate and combined medication could inhibit the cell invasion,promote apoptosis and reduce the protein expressions of p-Akt-Ser473 and DNMT3B(P< 0.05 to P< 0.01).Conclusions:The combined medication of Sorafenib with 5-nitrogen impurity-2'-deoxy cytidine can effectively reduce the sorafenib drug concentration and the protein expression levels of DNMT3B in hepatocellular carcinoma SMMC-7721 cells.