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Doxorubicin Activates Hepatitis B Virus Replication by Elevation of p21 (Waf1/Cip1) and C/EBPα Expression

Chen YF 1 , Chong CL 2 , Wu YC 3 , Wang YL 1 , Tsai KN 4 , Kuo TM 5 Show all authors , Hong MH 6 , Hu CP 7 , Chen ML 8 , Chou YC 9 , Chang C 1

Affiliations 

  • 1 Institute of Microbiology and Immunology, National Yang-Ming University, Taipei, Taiwan; Institute of Molecular and Genomic Medicine, National Health Research Institutes, Miaoli, Taiwan
  • 2 Faculty of Traditional Chinese Medicine, Southern University College, Johor Bahru, Malaysia
  • 3 Institute of Molecular and Genomic Medicine, National Health Research Institutes, Miaoli, Taiwan
  • 4 Institute of Molecular and Genomic Medicine, National Health Research Institutes, Miaoli, Taiwan; Institute of Molecular Medicine, National Tsing Hua University, Hsinchu, Taiwan
  • 5 Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan
  • 6 Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan
  • 7 Department of Life Science, Tunghai University, Taichung, Taiwan
  • 8 Center for Molecular Medicine, China Medical University and Hospital, Taichung, Taiwan
  • 9 Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan
PLoS One, 2015;10(6):e0131743.
PMID: 26121644 DOI: 10.1371/journal.pone.0131743

Abstract

Hepatitis B virus reactivation is an important medical issue in cancer patients who undergo systemic chemotherapy. Up to half of CHB carriers receiving chemotherapy develop hepatitis and among these cases a notable proportion are associated with HBV reactivation. However, the molecular mechanism(s) through which various chemotherapeutic agents induce HBV reactivation is not yet fully understood. In this study, we investigated the role of the cell cycle regulator p21 (Waf1/Cip1) in the modulation of HBV replication when a common chemotherapeutic agent, doxorubicin, is present. We showed that p21 expression was increased by doxorubicin treatment. This elevation in p21 expression enhanced the expression of CCAAT/enhancer-binding protein α (C/EBPα); such an increase is likely to promote the binding of C/EBPα to the HBV promoter, which will contribute to the activation of HBV replication. Our current study thus reveals the mechanism underlying doxorubicin modulation of HBV replication and provides an increased understanding of HBV reactivation in CHB patients who are receiving systemic chemotherapy.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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