title: Epirubicin directly promotes hepatitis B virus (HBV) replication in stable HBV-expressing cell lines: a novel mechanism of HBV reactivation following anticancer chemotherapy.
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.
authors.affiliation: Laboratory of Molecular Biology on Infectious Diseases, Ministry of Education, Second Affiliated Hospital, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Xu
authors.affiliation: Laboratory of Molecular Biology on Infectious Diseases, Ministry of Education, Second Affiliated Hospital, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Zeng
authors.initials: Z
authors.lastname: Tu
authors.affiliation: Laboratory of Molecular Biology on Infectious Diseases, Ministry of Education, Second Affiliated Hospital, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Ge
authors.initials: G
authors.lastname: Xu
authors.affiliation: Laboratory of Molecular Biology on Infectious Diseases, Ministry of Education, Second Affiliated Hospital, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Yuwei
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Microbiology and Immunology, North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China.
authors.forename: Wanlong
authors.initials: W
authors.lastname: Pan
authors.affiliation: Department of Pediatrics, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Xingxing
authors.initials: X
authors.lastname: Zhan
authors.affiliation: Laboratory of Molecular Biology on Infectious Diseases, Ministry of Education, Second Affiliated Hospital, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Luo
authors.affiliation: Laboratory of Molecular Biology on Infectious Diseases, Ministry of Education, Second Affiliated Hospital, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Laboratory of Molecular Biology on Infectious Diseases, Ministry of Education, Second Affiliated Hospital, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Juan
authors.initials: J
authors.lastname: Chen
authors.affiliation: Laboratory of Molecular Biology on Infectious Diseases, Ministry of Education, Second Affiliated Hospital, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Ailong
authors.initials: A
authors.lastname: Huang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004279:DNA, Viral / Q000378:metabolism; D004358:Drug Therapy; D015251:Epirubicin / Q000494:pharmacology*; D006515:Hepatitis B virus / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D019251:Nucleocapsid / Q000378:metabolism; D012367:RNA, Viral / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D014771:Virion / Q000378:metabolism; D014775:Virus Activation / Q000187:drug effects*; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; D004279:DNA, Viral; D012367:RNA, Viral; D015251:Epirubicin