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A Three-Dimensional Spheroid Model to Investigate the Tumor-Stromal Interaction in Hepatocellular Carcinoma
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Clinical-data-driven pharmacological framework in liver disease: From liver cirrhosis to hepatocellular carcinoma

Ki-Kwang Oh1, Goo-Hyun Kwon1, Jung-A Eom1

  • 1Institute for Liver and Digestive Diseases, College of Medicine, Hallym University, Chuncheon, 24252, South Korea.

British Journal of Pharmacology
|December 7, 2025
PubMed
Abstract

Insights

This study identified coronaridine hydroxyindolenine (CH) as a promising alkaloid candidate for liver cirrhosis (LC) and hepatocellular carcinoma (HCC). CH showed strong binding affinity to CCNB1, a key gene in liver cancer tissues.

Area of Science:

  • * Computational biology and bioinformatics
  • * Systems pharmacology
  • * Molecular docking and DFT analysis

Background:

  • * Liver cirrhosis (LC) and hepatocellular carcinoma (HCC) are significant health concerns.
  • * Adjacent non-tumour (ANT) tissues offer insights into the tumor microenvironment.
  • * Understanding molecular effectors and ligands is crucial for therapeutic development.

Purpose of the Study:

  • * To identify key molecular effectors and potential ligands in LC, HCC, and ANT tissues.
  • * To utilize clinical GEO data (GSE25097) within a systems pharmacology framework.
  • * To screen natural organic compounds (NOCs) for therapeutic potential.

Main Methods:

  • * Identification and visualization of differentially expressed genes (DEGs) using R and STRING.
  • * Construction of protein-protein interaction (PPI) networks.
  • * Screening of natural organic compounds (flavonoids, alkaloids), molecular docking, and DFT analyses.

Main Results:

  • * Identified 123 down-regulated and 146 up-regulated genes in LC, HCC, and ANT tissues.
  • * CCNB1, linked to the p53 pathway, was the most significantly upregulated gene.
  • * Coronaridine hydroxyindolenine (CH), an alkaloid, demonstrated superior binding affinity to CCNB1 compared to flavopiridol.

Conclusions:

  • * The CH-CCNB1 complex exhibits high stability.
  • * CH is a potential therapeutic candidate for further investigation against LC, HCC, and ANT.
  • * This study highlights the potential of systems pharmacology in identifying novel drug leads.
Keywords:
CCNB1GSE25097adjacent non‐tumour tissuecoronaridine hydroxyindoleninehepatocellular carcinomaliver cirrhosisp53 signalling pathway

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