title: Metformin inhibits hepatitis B virus protein production and replication in human hepatoma cells.
abstract: Hepatitis B virus surface antigen (HBsAg) plays an important role in maintaining the tolerance and may interfere with host innate and adaptive immune responses; therefore, novel therapeutic strategies to reduce HBsAg loads in patients infected with hepatitis B virus (HBV) are emerging as an attractive but challenging issue. Metformin could regulate hepatic metabolism while the latter interacts with HBV infection. We hypothesized that metformin could affect HBsAg expression and HBV replication and may work synergistically when combined with current antivirals. In our study, a notably inhibitory effect on HBsAg production, as well as a moderate inhibition in HBV replication and HBeAg expression was observed following metformin treatment. The 50% effective concentration (EC50) for extracellular HBsAg and intracellular HBsAg in HBV-producing HepG2.2.15 cells was 2.85 mm and 2.75 mm, respectively, with a similarly selective index of about 18. When administered in combination, metformin enhanced the inhibitory effects of interferon-α2b on HBsAg expression and HBV replication and provided a complimentary role in HBsAg expression for lamivudine (LMV). This novel action of metformin derives partially from its inhibition on multiple HBV cis-acting elements. By the virtues of preferably hepatocyte distribution and safety profile, collectively, our results suggest that metformin would be potentially clinically helpful as an HBsAg production inhibitor.
authors.affiliation: Department of Infectious Diseases, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, China; Key Laboratory of Medical Molecular Virology of the Ministries of Education and Health, Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China; Department of Liver Diseases, The Sixth People's Hospital affiliated to Zhejiang University of Traditional Chinese Medicine, Hangzhou, Zhejiang, China.
authors.forename: Y-H
authors.initials: YH
authors.lastname: Xun
authors.forename: Y-J
authors.initials: YJ
authors.lastname: Zhang
authors.forename: Q-C
authors.initials: QC
authors.lastname: Pan
authors.forename: R-C
authors.initials: RC
authors.lastname: Mao
authors.forename: Y-L
authors.initials: YL
authors.lastname: Qin
authors.forename: H-Y
authors.initials: HY
authors.lastname: Liu
authors.forename: Y-M
authors.initials: YM
authors.lastname: Zhang
authors.forename: Y-S
authors.initials: YS
authors.lastname: Yu
authors.forename: Z-H
authors.initials: ZH
authors.lastname: Tang
authors.forename: M-J
authors.initials: MJ
authors.lastname: Lu
authors.forename: G-Q
authors.initials: GQ
authors.lastname: Zang
authors.forename: J-M
authors.initials: JM
authors.lastname: Zhang
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D058492:Drug Repositioning; D056945:Hep G2 Cells; D006514:Hepatitis B Surface Antigens / Q000096:biosynthesis; D006515:Hepatitis B virus / Q000187:drug effects* / Q000502:physiology; D022781:Hepatocytes / Q000821:virology*; D006801:Humans; D008687:Metformin / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D006514:Hepatitis B Surface Antigens; D008687:Metformin
keywords: hepatitis B virus; hepatitis B virus (HBV) surface antigen; metformin; production; transcriptional regulation