ArticleVirology journal2020
Mitomycin, 5-fluorouracil, leflunomide, and mycophenolic acid directly promote hepatitis B virus replication and expression in vitro.
Article in Virology journal, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 13 citations in OpenAlex.
- The interplay between hepatitis B virus and antitumor drugs in the treatment of hepatocellular carcinoma.Clinical and experimental medicine · 2025Review
- Oral Prednisolone, Apremilast and Human Umbilical Cord Mesenchymal Stem Cells in the Management of Pemphigus Foliaceus.Journal of inflammation research · 2025Article
- Plants against cancer: the immune-boosting herbal microbiome: not of the plant, but in the plant. Basic concepts, introduction, and future resource for vaccine adjuvant discovery.Frontiers in oncology · 2023Review
- COVID-19 was not associated or trigger disease activity in spondylarthritis patients: ReumaCoV-Brasil cross-sectional data.Advances in rheumatology (London, England) · 2022Article
- What role for cellular metabolism in the control of hepatitis viruses?Frontiers in immunology · 2022Review
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Authors and funding
6 authors at 2 institutions in 1 country.
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Abstract
backgroundReactivation of hepatitis B virus is a common complication that occurs in patients with hepatitis B virus (HBV) infection who have received cytotoxic chemotherapy or immunosuppressive therapy. This clinical phenomenon not only occurs in overt HBV infection patients but also occurs in patients with resolved HBV infection. Previous research has confirmed that epirubicin and dexamethasone can stimulate HBV replication and expression directly rather than indirectly through immunosuppression. Mitomycin and 5-fluorouracil are currently used as cytotoxic chemotherapy drugs for cancer patients. Leflunomide and mycophenolic acid are regarded as immunosuppressants for autoimmune diseases, and numerous clinical studies have reported that these drugs can reactivate HBV replication. In this study, we aimed to investigate whether mitomycin, 5-fluorouracil, leflunomide and mycophenolic acid induce HBV reactivation directly rather than indirectly through immunosuppression.
methodsTo observe the effect of mitomycin, 5-fluorouracil, leflunomide and mycophenolic acid on HBV replication and expression, we employed HepG2.2.15 and HBV-NLuc-35 cells as a cell model. Next, by native agarose gel electrophoresis (NAGE), quantitative PCR (qPCR), luciferase assay and HBV e antigen (HBeAg) enzyme-linked immunosorbent assay (ELISA) we detected changes in HBV replication and expression induced by these drugs. We also investigated whether lamivudine could inhibit the observed phenotype. SPSS 18.0 software was employed for statistical analysis, One-way ANOVA was used to compare multiple groups.
resultsExpression of HBV capsids and HBeAg in HepG2.2.15 cells was increased by increasing concentration of mitomycin, 5-fluorouracil, leflunomide, and mycophenolic acid. This phenomenon was also demonstrated in HBV-NLuc-35 cells, and the expression of capsids and luciferase activity increased in the same concentration-dependent manner. Replication levels of intracellular capsid DNA and extracellular HBV DNA in HepG2.2.15 cells gradually increased in a dose-dependent manner. In addition, although epirubicin, mitomycin, 5-fluorouracil, dexamethasone, leflunomide and mycophenolic acid enhanced HBV replication, lamivudine inhibited this process.
conclusionOur study confirmed that mitomycin, 5-fluorouracil, leflunomide and mycophenolic acid directly upregulated HBV replication and expression in vitro. This effect was investigated not only in HepG2.2.15 cells but also in the HBV-NLuc-35 replication system. Moreover, this effect could be prevented by nucleoside analogs, such as lamivudine (LAM). Thus, for patients with HBV infection, prophylactic antiviral therapy is necessary before receiving cytotoxic chemotherapy or immunosuppressive therapy.
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