Sorafenib suppresses hepatitis B virus gene expression via inhibiting JNK pathway

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 Χ1.3 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.