ArticleJournal of experimental & clinical cancer research : CR2019
Metformin inhibits metastatic breast cancer progression and improves chemosensitivity by inducing vessel normalization via PDGF-B downregulation.
Article in Journal of experimental & clinical cancer research : CR, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers, 3 of them syntheses that pooled it.
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Who cites it
90 citing papers in PubMed, 3 syntheses or guidelines pooled it, 139 citations in OpenAlex.
- Antiproliferative Mechanisms of Metformin in Breast Cancer: A Systematic Review of the Literature.International journal of molecular sciences · 2024Pooled it
- Prognostic value of metformin in cancers: An updated meta-analysis based on 80 cohort studies.Medicine · 2022 · on this mapPooled it
- Statin and metformin use and outcomes in patients with castration-resistant prostate cancer treated with enzalutamide: A meta-analysis of AFFIRM, PREVAIL and PROSPER.European journal of cancer (Oxford, England : 1990) · 2022Pooled it
- Clinical utilities of platelet-derived growth factor signaling in breast cancer.Pharmacological research · 2026Review
- p53 and p21 Status Influences Cellular Response to Metformin inCurrent issues in molecular biology · 2026Article
- Deciphering the Anti-Tumor Mechanisms of Metformin Through Reprogramming of the Tumor Microenvironment.Cells · 2026Review
- Lactate metabolism and lactylation: Therapeutic and pre-clinical implications in neovascularization in peripheral artery disease.Journal of pharmaceutical analysis · 2026Review
- Pericytes and mesenchymal stromal cells converge toward pro-tumor phenotypes in the tumor microenvironment.Discover oncology · 2026Review
- Immunoregulatory effect of metformin in monocytes exposed to SARS-CoV-2 spike protein subunit 1.Immunometabolism (Cobham, Surrey) · 2026Article
- Combination of metformin and parthenolide inhibits breast cancer in mice by apoptosis induction and angiogenesis inhibition.Frontiers in immunology · 2026Article
- Abietic Acid Induces DNA Damage and Cell Apoptosis in Lung Cancer Cells Through Targeting TOP2A.Biomolecules · 2025Article
- Immunoregulatory effect of metformin in monocytes exposed to SARS-CoV-2 spike protein subunit 1.bioRxiv : the preprint server for biology · 2025Article
- SPANXB1 drives brain metastasis in breast cancer via MMP1 regulation: potential therapeutic insights with metformin.Cell death discovery · 2025Article
- Single-Cell Transcriptomic Analysis Unveils Key Regulators and Signaling Pathways in Lung Adenocarcinoma Progression.Biomedicines · 2025Article
- Blockade of Exosome Release Sensitizes Breast Cancer to Doxorubicin via Inhibiting Angiogenesis.Cancer medicine · 2025Article
- Biguanides antithetically regulate tumor properties by the dose-dependent mitochondrial reprogramming-driven c-Src pathway.Cell reports. Medicine · 2025Article
- Repurposing of Metabolic Drugs Metformin and Simvastatin as an Emerging Class of Cancer Therapeutics.Pharmaceutical research · 2025Review
- Hypoxia-driven angiogenesis and metabolic reprogramming in vascular tumors.Frontiers in cell and developmental biology · 2025Review
- Metformin and its Nanoformulations in Cancer Prevention and Therapy.Current pharmaceutical design · 2025Review
- Extinguishing the flames of inflammation: retardant effect of chlorquinaldol on NLRP3-driven diseases.Molecular medicine (Cambridge, Mass.) · 2024Article
30 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
Abstract
backgroundVascular maturity and functionality are closely associated with tumor progression and chemosensitivity. The antidiabetic agent metformin has shown its ability to inhibit tumor angiogenesis in metastatic breast cancer models. However, it remains unclear if or how metformin remodels the abnormal vasculature of metastatic breast cancer, while inhibiting angiogenesis.
methodsMetastatic breast cancer models were constructed to compare microvessel density (MVD), vascular maturity and function, lung metastasis and chemosensitivity in metformin-treated or untreated mice. Protein array assay and transcriptome sequencing were performed for genetic screening. Lentiviral shRNA-PDGF-B transfection was used for observing the contribution of PDGF-B knockdown to metformin's vascular effects.
resultsMetastatic breast cancers were characterized by an excessively angiogenic, immature and morphologically abnormal vasculature. Compared to control, metformin significantly reduced MVD, leakage and hypoxia, and increased vascular mural cells coverage and perfusion, namely, "vessel normalization". Metformin at human blood concentrations had no direct effect on the migration and proliferation of cancer cells. Based on that, reduced lung metastasis of the primary tumor and improved chemosensitization by metformin were assumed to be mediated via metformin's vascular effects. Further results of genetic screening and in vivo experiments showed that the downregulation of platelet-derived growth factor B (PDGF-B) greatly contributed to the metformin-induced vessel normalization.
conclusionsThese findings provide pre-clinical evidences for the vascular mechanism of metformin-induced metastasis inhibition and the chemosensitization of metastatic breast cancers.
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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.