Epirubicin directly promotes hepatitis B virus (HBV) replication in stable HBV-expressing cell lines: A novel mechanism of HBV reactivation following anticancer chemotherapy

Xu,Lei; Tu,Zeng; Xu,Ge; Wang,Yuwei; Pan,WanLong; Zhan,XingXing; Luo,Qiang; Huang,Yuan; Chen,Juan; Huang,AiLong

doi:10.3892/mmr.2014.1973

Epirubicin directly promotes hepatitis B virus (HBV) replication in stable HBV-expressing cell lines: A novel mechanism of HBV reactivation following anticancer chemotherapy

Authors:
- Lei Xu
- Zeng Tu
- Ge Xu
- Yuwei Wang
- WanLong Pan
- XingXing Zhan
- Qiang Luo
- Yuan Huang
- Juan Chen
- AiLong Huang
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Affiliations: Laboratory of Molecular Biology on Infectious Diseases, Ministry of Education, Second Affiliated Hospital, Chongqing Medical University, Chongqing 400016, P.R. China, Laboratory of Molecular Biology on Infectious Diseases, Ministry of Education, Second Affiliated Hospital, Chongqing Medical University, Chongqing 400016, P.R. China, Department of Microbiology and Immunology, North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China, Department of Pediatrics, Chongqing Medical University, Chongqing 400016, P.R. China
Published online on: February 20, 2014 https://doi.org/10.3892/mmr.2014.1973
Pages: 1345-1350

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Abstract

Chronic hepatitis B virus (HBV) infection is a worldwide problem and HBV reactivation following anticancer chemotherapy has become an emerging clinical challenge. However, the mechanisms of HBV reactivation following chemotherapy remain unclear. Epirubicin is an anthracycline drug used in chemotherapy to treat numerous types of malignancy, including breast cancer, acute leukemia, malignant lymphoma, lung cancer, ovarian cancer and stomach cancer. Epirubicin acts by intercalating DNA strands and inhibiting DNA and RNA synthesis. In this study, it was demonstrated that epirubicin directly upregulated the levels of in vitro HBV replication in a concentration‑dependent manner. Exposure to epirubicin for 24 h induced >11- and 6-fold increases in the levels of intracellular and secreted HBV DNA, respectively. In concordance with the elevated levels of HBV DNA, the expression levels of HBV pregenomic RNA, intracellular HBV surface and HBV core antigens, and secreted HBV e antigen were significantly increased by treatment with 0.5 µM epirubicin. Notably, epirubicin promoted cellular excretion of HBV nucleocapsids, which are closely associated with the pathological effects of HBV, including acute liver failure. In conclusion, epirubicin exhibited a direct stimulatory effect on HBV replication and this may be a novel mechanism of HBV reactivation following cytotoxic anticancer chemotherapy.

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