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Mechanism of atorvastatin in treating hepatocellular carcinoma: a study based on network pharmacology, molecular

Youwen Hu1, Yangyang Xiao2

  • 1Department of Gastroenterology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China.

Naunyn-Schmiedeberg'S Archives of Pharmacology
|November 28, 2024
PubMed

Insights

Atorvastatin may treat hepatocellular carcinoma (HCC) by targeting CYP2C9. This study identified CYP2C9 as a key gene, showing its reduced expression in HCC and association with better patient prognosis.

Area of Science:

  • Oncology
  • Pharmacology
  • Bioinformatics

Background:

  • Hepatocellular carcinoma (HCC) presents significant morbidity and mortality.
  • Statins, including atorvastatin, show potential in HCC prevention and treatment, but underlying mechanisms require elucidation.
  • Limited research exists on the specific mechanisms of atorvastatin in HCC treatment.

Purpose of the Study:

  • To elucidate the mechanism of atorvastatin in treating hepatocellular carcinoma (HCC).
  • To identify potential therapeutic targets of atorvastatin for HCC using network pharmacology and bioinformatics.

Main Methods:

  • Utilized network pharmacology and bioinformatics analyses on public databases (SwissTargetPrediction, PharmMapper, DrugBank, GSE datasets, TCGA, HPA).
  • Identified differentially expressed genes (DEGs) in HCC and atorvastatin targets, followed by intersection analysis.
  • Performed protein-protein interaction (PPI) analysis, hub gene identification (Cytoscape, LASSO), survival analysis (Kaplan-Meier, Cox), pathway analysis (KEGG, GSEA), and molecular docking.

Main Results:

  • Identified 79 potential targets for atorvastatin in HCC treatment from intersecting DEGs and drug targets.
  • Pinpointed Cytochrome P450 Family 2 Subfamily C Member 9 (CYP2C9) as the key hub gene, showing reduced expression in HCC tissues.
  • Demonstrated that high CYP2C9 expression correlates with favorable HCC patient prognosis and identified xenobiotic metabolism pathways as key mechanisms.

Conclusions:

  • CYP2C9 is a potential therapeutic target for atorvastatin in hepatocellular carcinoma (HCC) treatment.
  • Atorvastatin's efficacy in HCC may involve the regulation of CYP2C9 and associated metabolic pathways.
  • CYP2C9 expression serves as a prognostic biomarker for HCC patients.
Keywords:
AtorvastatinBioinformatic analysisCYP2C9Hepatocellular carcinomaNetwork pharmacology

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