ArticleOncotarget2017
Metformin-treated cancer cells modulate macrophage polarization through AMPK-NF-κB signaling.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 115 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
115 citing papers in PubMed, 1 synthesis or guideline pooled it, 188 citations in OpenAlex.
- From mechanism to therapy: advances in macrophage polarisation and targeted intervention in osteosarcoma.Frontiers in immunology · 2026Pooled it
- A Randomized Study on the Effect of Metformin Combined with Intensive-Exercise Diet Therapy on Glucose and Lipid Metabolism and Islet Function in Patients with Renal Cell Carcinoma and Diabetes.Disease markers · 2022Trial
- Comparative Effects of Metformin, Boric Acid, and Lithium Chloride on Oxidative Stress-Mediated Cytotoxicity in HepG2 Hepatocarcinoma Cells.Biological trace element research · 2026Article
- Therapeutic repurposing of old drugs to modulate the tumor immune microenvironment and enhance immunotherapy efficacy.Journal of pharmaceutical analysis · 2026Review
- Deciphering the Anti-Tumor Mechanisms of Metformin Through Reprogramming of the Tumor Microenvironment.Cells · 2026Review
- Metformin as an Innate Immune Modulator: Metabolic and Epigenetic Reprogramming of Innate Immune Cells and Therapeutic Implications.Current issues in molecular biology · 2026Review
- Macrophage-centered immunotherapy for osteosarcoma: mechanisms, repolarization, and translational strategies.World journal of surgical oncology · 2026Review
- Metformin Use and Development of Esophageal Squamous Cell Carcinoma.JAMA network open · 2026Article
- Dynamic magneto-mechanical force in lysosomes induces durable macrophage repolarization for antitumor immunity.Cell research · 2026Article
- Metabolic reprogramming in cancer: signaling pathways and therapeutic targets.Molecular cancer · 2026Review
- Metformin glycyrrhetinic acid binary injectable hydrogel for synergistic tumor immunotherapy via spatiotemporal microenvironment remodeling.Materials today. Bio · 2026Article
- Immune-Centered Cross-Talk Between Cancer Cells and the Tumor Microenvironment-Implications for Therapy.Cancers · 2026Review
- Blood vessels as primary site of rejection in murine lung transplantation.Transplant international : official journal of the European Society for Organ Transplantation · 2026Article
- Metformin modulates the phenotypes of tumor-associated macrophages in glioblastoma in a context-dependent manner by promoting the homeostasis of macrophages.Frontiers in oncology · 2026Article
- Macrophage and IL-6 signaling modulate multiple myeloma progression and response to metformin and CAR-T cell therapy.Frontiers in immunology · 2026Article
- Fluid Shear Stress Modulates Inflammation in Breast Cancer Microenvironment.Diseases (Basel, Switzerland) · 2025Article
- Metformin improves CD8+ T cell responses and parasitemia control via macrophage modulation during Trypanosoma cruzi infection.Journal of leukocyte biology · 2025Article
- Hierarchical metal exposure in umbilical cord blood in relation to oxidative stress and AMPK/NF-κB signaling in preterm membrane rupture.Scientific reports · 2025Article
- In vitro Evaluation of Zinc Oxide-Metformin Folic Acid Nanocomposite as a Targeted Drug Delivery System for Cancer Therapy.Asian Pacific journal of cancer prevention : APJCP · 2025Article
- Metabolic Signaling in the Tumor Microenvironment.Cancers · 2025Review
55 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Accumulating evidence is indicating metformin to possess the potential ability in preventing tumor development and suppressing cancer growth. However, the exact mechanism of its antitumorigenic effects is still not clear. We found that metformin suppressed the ability of cancer to skew macrophage toward M2 phenotype. Metformin treated cancer cells increased macrophage expression of M1-related cytokines IL-12 and TNF-α and attenuated M2-related cytokines IL-8, IL-10, and TGF-β expression. Furthermore, metformin treated cancer cells displayed inhibited secretion of IL-4, IL-10 and IL-13; cytokines important for inducing M2 macrophages. Conversely, M1 inducing cytokine IFN-γ was upper-regulated in cancer cells. Additionally, through increasing AMPK and p65 phosphorylation, metformin treatment activated AMPK-NF-κB signaling of cancer cells that participate in regulating M1 and M2 inducing cytokines expression. Moreover, Compound C, an AMPK inhibitor, significantly increased IL-4, IL-10, and IL-13 expression while BAY-117082, an NF-κB inhibitor, decreased expression. In metformin-treated tumor tissue, the percentage of M2-like macrophages decreased while M1-like macrophages increased. These findings suggest that metformin activates cancer AMPK-NF-κB signaling, a pathway involved in regulating M1/M2 expression and inducing genes for macrophage polarization to anti-tumor phenotype.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.