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Updated: Jun 27, 2025

Studying Pancreatic Cancer Stem Cell Characteristics for Developing New Treatment Strategies
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Low-dose metformin suppresses hepatocellular carcinoma metastasis via the AMPK/JNK/IL-8 pathway

Chengwen Zhao1, Lu Zheng1, Yuting Ma1

  • 1Department of Clinical Laboratory, Xuzhou Institute of Medical Science, Xuzhou Central Hospital, Xuzhou, China.

International Journal of Immunopathology and Pharmacology
|April 28, 2024
PubMed
Abstract

Insights

Low-dose metformin inhibits hepatocellular carcinoma (HCC) metastasis by suppressing interleukin-8 (IL-8) expression. Targeting the AMPK/JNK/IL-8 pathway offers a potential treatment strategy for advanced HCC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Interleukin-8 (IL-8) is implicated in cancer development and metastasis.
  • Metformin, an oral hypoglycemic drug, shows potential antitumour activity.
  • The effect of metformin on IL-8 in hepatocellular carcinoma (HCC) is not well understood.

Purpose of the Study:

  • To investigate the effect of metformin on IL-8 expression in HCC.
  • To determine if metformin can inhibit IL-8 to impede HCC progression.

Main Methods:

  • Measured IL-8 levels in HCC patient plasma and cell lines via flow cytometry.
  • Validated IL-8 expression using the Human Protein Atlas database.
  • Analyzed IL-8 prognostic value and immune checkpoint correlations using Kaplan-Meier Plotter, TIMER, and TCGA databases.
  • Investigated metformin's molecular mechanism via bioinformatics, western blotting, and transwell assays.

Main Results:

  • Elevated IL-8 expression in HCC patients and cells correlated with poor prognosis and immune checkpoints.
  • Low-dose metformin inhibited IL-8 secretion and HCC cell migration.
  • Metformin suppressed HCC metastasis via the AMPK/JNK/IL-8/MMP9 pathway.

Conclusions:

  • Low-dose metformin inhibits HCC metastasis by reducing IL-8 expression.
  • The AMPK/JNK/IL-8 axis presents a potential therapeutic target for HCC metastasis.
Keywords:
IL-8hepatocellular carcinomaimmune checkpointmetastasismetformin

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