ABSTRACT
Objective To investigate the function of sorafenib on the growth of hepatocellular carcinoma by establishing subcutaneous transplantation tumor model with nude mice.To explore the effect of sorafenib on circadian clock gene expression in hepatoma cells.Methods Mouse tumor model was established by implanting hepatocarcinoma cell (HepG2) subcutaneously in Balb/C nude mice.Sixteen experimental mice were randomly divided into two groups:sorafenib treatment group (n =8) and solvent control group (n =8).The nude mice were treated with sorafenib (100 mg/kg) and DMSO daily by intragastric administration,respectively.The volume of tumors was recorded every 3 days.The expressions level of circadian clock genes (Per1,Per2,Per3,CLOCK,Cry1,Cry2,BMAL1 and CKIε) were detected by real-time polymerase chain reaction (Real-time PCR).The correlations between the size of the xenografts and the expressions of the circadian clock genes were further analyzed.Results Compared with the control group,the tumor size in the sorafenib treatment group were significantly smaller comparing with the control group.Results of Real-time PCR showed that the expression level of Per1,Cry1 and BMAL1 mRNA was remarkably decreased in the treatment group (Per1,P =0.02;Cry1,P =0.002;BMAL1,P =0.035),the differences were statistically significant.Correlation analysis showed that the size of subcutaneous transplantation tumorsin nude mice was negatively correlated with the expressions of Per1,Per2,Cry1 and Cry2 mRNA in control group.While,the size of subcutaneous transplantation tumors was negatively correlated with the expressions of Per2,Per3 and BMAL1 levels in the sorafenib treatment group.Conclusions There is a negative correlation between the expression levels of some biological clock genes and the size of transplantation tumor in nude mice.Sorafenib treatment significantly inhibited the growth of hepatocellular carcinoma in nude mice and down-regulation the expressions of Per1,Cry1 and BMAL1 mRNA in hepatoma cells.