Page 104 - Read Online

Original Article

Sorafenib suppresses hepatitis B virus gene expression via
Sorafenib suppresses hepatitis B virus gene expression via
inhibiting JNK pathway
inhibiting JNK pathway

Hyun Kook Cho , Ju Ran Kim , So Young Kim , Yi Yi Kyaw , Aye Aye Win ,
1
1
1
2
2
Jae Hun Cheong 1
1 Department of Molecular Biology, Pusan National University, Busan 609-735, South Korea
2 Department of Medical Research (Lower Myanmar), Experimental Medicine Research Division , Yangon 11191, Myanmar
ABSTRACT
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.

Key words: Sorafenib; hepatitis B virus; JNK; farnesoid X receptor; antiviral effect

Address for correspondence:
Address for correspondence:
Prof. Jae Hun Cheong, Department of Molecular Biology, Pusan National University, Busan 609-735, South Korea.
E-mail: molecule85@pusan.ac.kr
Received: 04-02-2015, Accepted: 27-04-2015

INTRODUCTION HBV reactivation. HBV reactivation can be transient and
resolve spontaneously but often leads to clinically apparent
Hepatitis B virus (HBV) infection is a serious public health acute hepatitis. Its occurrence constantly results in delays
problem with approximately 350 million people with chronic in chemotherapy schedules and disruption of cytotoxic
HBV infection in the world. Among HBV-infected patients, treatment regimens and in the most severe cases, leads to
15-40% develop cirrhosis, liver failure, and hepatocellular acute liver failure and death. Although HBV reactivation
[2]
carcinoma (HCC). Persistent infection with HBV is a leading can be prevented by antiviral prophylaxis, the mechanism
[1]
cause of human chronic liver disease. It is well known that by which HBV contributes to events leading to liver injury in
for cancer patients with chronic HBV infection who are chronic HBV carriers who are receiving cancer chemotherapy
undergoing cytotoxic chemotherapy, hepatic dysfunction remains to be fully understood.
occurs more frequently than that of non-HBV carriers, and
this has been attributed mainly to the development of Sorafenib (BAY43-9000, Nexavar) is the first and only
medication approved by the USA Food and Drug Administration
Access this article online
Quick Response Code for the treatment of advanced HCC. Sorafenib is a multikinase
Website: inhibitor which has been shown to block tumor cell
http://www.hrjournal.net/ proliferation and angiogenesis by inhibiting serine/threonine
kinases (c-RAF and b-RAF) as well as several receptor tyrosine
[3]
kinases. Although several drugs with high efficacy against
DOI:
10.4103/2394-5079.158391 chronic hepatitis B (CHB) are currently approved in the USA
for the treatment of CHB, the drugs have adverse effects

Hepatoma Research | Volume 1 | Issue 2 | July 15, 2015 97