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In Vitro Cultivation Techniques for Modeling Liver Organogenesis, Building Assembloids, and Designing Synthetic Tissues using Human Cell Lines
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In Vitro Cultivation Techniques for Modeling Liver Organogenesis, Building Assembloids, and Designing Synthetic Tissues using Human Cell Lines

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Azvudine Suppresses Epithelial-Mesenchymal Transition in Hepatocellular Carcinoma by Targeting the Notch-HEY

Yao Meng1,2, Peiyi Sun1,2, Yixin Ren3

  • 1Beijing Key Laboratory of Technology and Application for Anti-Infective New Drugs Research and Development/Laboratory of Pharmacology, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.

International Journal of Molecular Sciences
|June 13, 2025
PubMed

Insights

Azvudine (FNC) inhibits liver cancer cell migration by targeting Jagged1 and downregulating epithelial-mesenchymal transition (EMT) markers. This antiviral drug shows promise for hepatocellular carcinoma (HCC) treatment by interfering with key cancer pathways.

Area of Science:

  • Oncology
  • Virology
  • Molecular Biology

Background:

  • Azvudine (FNC), an antiviral cytidine analogue, has shown anticancer effects in various cell lines.
  • Its efficacy and mechanisms in hepatocellular carcinoma (HCC) remain largely unexplored.
  • Epithelial-mesenchymal transition (EMT) is a critical process in cancer progression and metastasis.

Purpose of the Study:

  • To investigate the anti-EMT activity of Azvudine (FNC) in hepatocellular carcinoma (HCC).
  • To elucidate the molecular mechanisms underlying FNC's effects on liver cancer cells.
  • To evaluate FNC's potential as a therapeutic agent for HCC.

Main Methods:

  • Utilized the Huh7 liver cancer cell line to assess FNC's impact on cell migration.
  • Analyzed key EMT markers (MMPs, E-cadherin) at transcriptional and protein levels.
  • Employed microscale thermophoresis (MST) and molecular dynamics (MD) simulations to identify FNC's molecular target.

Main Results:

  • FNC significantly inhibited Huh7 cell migration.
  • FNC downregulated crucial EMT markers, including MMPs and E-cadherin.
  • FNC was found to directly bind to Jagged1, a key component of the Notch signaling pathway implicated in HCC.

Conclusions:

  • Azvudine (FNC) exhibits anti-EMT activity and inhibits hepatocellular carcinoma (HCC) cell migration.
  • FNC targets Jagged1, suggesting a novel therapeutic mechanism for HCC.
  • FNC demonstrates significant potential for HCC treatment, warranting further clinical investigation.
Keywords:
EMTFNCHCC treatmentHEY proteinsNotch signalling pathway

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