Journal of Clinical and Translational Hepatology

Journal of Clinical and Translational Hepatology

Thursday, 05 / 13 / 2021

Articles

Abstract

ORIGINAL ARTICLE

Histone Deacetylase Inhibitors Romidepsin and Vorinostat Promote Hepatitis B Virus Replication by Inducing Cell Cycle Arrest

Yang Yang1,#, Yu Yan1,#, Zhen Chen1,#, Jie Hu1, Kai Wang1Ni Tang1, Xiaosong Li2,* and Zhi Zhou3,*

1  Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
2  Clinical Molecular Medicine Testing Center, The First Affiliated Hospital, Chongqing Medical University, Chongqing, China
3  Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
#These authors contributed equally to this work.
*Correspondence to: Xiaosong Li, Clinical Molecular Medicine Testing Center, The First Affiliated Hospital, Chongqing Medical University, Chongqing 400010, China. Tel: +86-23-68486780, E-mail: This email address is being protected from spambots. You need JavaScript enabled to view it. ;Zhi Zhou, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, China. Tel: +86-23-62887067, E-mail:  This email address is being protected from spambots. You need JavaScript enabled to view it.

Journal of Clinical and Translational Hepatology 2021;9(2):160-168 DOI: 10.14218/JCTH.2020.00105
Received: November 11, 2020 Accepted: February 24, 2021 Published online: March 8, 2021

Abstract

Background and Aims: Chronic hepatitis B virus (HBV) infection is a global public health challenge. HBV reactivation usually occurs in cancer patients after receiving cytotoxic chemotherapy or immunosuppressive therapies. Romidepsin (FK228) and vorinostat (SAHA) are histone deacetylase inhibitors (HDACi) approved by the Food and Drug Administration as novel antitumor agents. The aim of this study was to explore the effects and mechanisms of HDACi treatment on HBV replication.

Methods: To assess these effects, human hepatoma cell lines were cultured and cell viability after FK228 or SAHA treatment was measured by the CCK-8 cell counting kit-8 assay. Then, HBV DNA and RNA were quantified by real-time PCR and Southern blotting. Furthermore, analysis by western blotting, enzyme-linked immunosorbent assay (ELISA), immunohistochemistry, and flow cytometry was performed.

Results: FK228/SAHA treatment significantly promoted HBV replication and biosynthesis in both HBV-replicating cells and HBV-transgenic mouse model. Flow cytometry assay indicated that FK228/SAHA enhanced HBV replication by inducing cell cycle arrest through modulating the expression of cell cycle regulatory proteins. In addition, simultaneous inhibition of HDAC1/2 by FK228 promoted HBV replication more effectively than the broad spectrum HDAC inhibitor SAHA.

Conclusions: Overall, our results demonstrate that cell cycle blockage plays an important role in FK228/SAHA-enhanced HBV replication, thus providing a potential avenue for rational use of HDACi in patients with chronic hepatitis B.

Keywords

HBV reactivation, Histone deacetylase inhibitor, Romidepsin, Vorinostat, Cell cycle

Journal of Clinical and Translational Hepatology 2021 vol. 9, 160-168  [ Html  ] [ PDF Full-text ]

© 2021 Authors. This is an Open Access article distributed under the terms of the  Creative Commons Attribution-Noncommercial 4.0 License(CC BY-NC 4.0), permitting all non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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