Aim:Hepatitis B virus(HBV)infection is a major cause of chronic liver diseases.Sorafenib is a multikinase inhibitor and an approved anti-liver cancer drug.Here we demonstrated the antiviral effect of sorafenib on HBV ...Aim:Hepatitis B virus(HBV)infection is a major cause of chronic liver diseases.Sorafenib is a multikinase inhibitor and an approved anti-liver cancer drug.Here we demonstrated the antiviral effect of sorafenib on HBV gene expression.Methods:To investigate the effect of sorafenib on HBV gene expression,a luciferase assay was performed with×1.3 Cp-luciferase HBV construct and reverse transcriptase polymerase chain reaction(PCR),real-time PCR,and Western blotting analyses were performed using HepG2 cells derived from hepatocellular carcinoma and Chang liver cells derived from a normal liver tissue.Results:Sorafenib suppressed HBV gene expression via inhibiting the JNK pathway.In this process,the farnesoid X receptor(FXR),a transcription factor that has been reported to increase HBV replication and gene expression,was under control of the JNK pathway.Notably,JNK activation increased FXR protein levels,not mRNA levels.Conclusion:Sorafenib suppressed HBV gene expression via inhibiting the JNK pathway,which regulates FXR activity.展开更多
基金This work was supported by a 2-Year Research Grant of Pusan National University.
文摘Aim:Hepatitis B virus(HBV)infection is a major cause of chronic liver diseases.Sorafenib is a multikinase inhibitor and an approved anti-liver cancer drug.Here we demonstrated the antiviral effect of sorafenib on HBV gene expression.Methods:To investigate the effect of sorafenib on HBV gene expression,a luciferase assay was performed with×1.3 Cp-luciferase HBV construct and reverse transcriptase polymerase chain reaction(PCR),real-time PCR,and Western blotting analyses were performed using HepG2 cells derived from hepatocellular carcinoma and Chang liver cells derived from a normal liver tissue.Results:Sorafenib suppressed HBV gene expression via inhibiting the JNK pathway.In this process,the farnesoid X receptor(FXR),a transcription factor that has been reported to increase HBV replication and gene expression,was under control of the JNK pathway.Notably,JNK activation increased FXR protein levels,not mRNA levels.Conclusion:Sorafenib suppressed HBV gene expression via inhibiting the JNK pathway,which regulates FXR activity.
