ArticlePloS one2017
Metformin inhibits the development, and promotes the resensitization, of treatment-resistant breast cancer.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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
23 citing papers in PubMed, 55 citations in OpenAlex.
- Metformin and its Nanoformulations in Cancer Prevention and Therapy.Current pharmaceutical design · 2025Review
- Changes in the Sensitivity of MCF-7 and MCF-7/DX Breast Cancer Cells to Cytostatic in the Presence of Metformin.Molecules (Basel, Switzerland) · 2024Article
- Article
- Chromatin modifiers in human disease: from functional roles to regulatory mechanisms.Molecular biomedicine · 2024Review
- Metformin and Breast Cancer: Current Findings and Future Perspectives from Preclinical and Clinical Studies.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Estrogen Receptor Is Required for Metformin-Induced Apoptosis in Breast Cancer Cells Under Hyperglycemic Conditions.Breast cancer : basic and clinical research · 2024Article
- Implications of BCRP modulation on PTZ-induced seizures in mice: Role of ko143 and metformin as adjuvants to lamotrigine.Naunyn-Schmiedeberg's archives of pharmacology · 2023Article
- Article
- The promising therapeutic effects of metformin on metabolic reprogramming of cancer-associated fibroblasts in solid tumors.Cellular & molecular biology letters · 2022Article
- Metformin and Cancer, an Ambiguanidous Relationship.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Transcriptional and H3K27ac related genome profiles in oral squamous cell carcinoma cells treated with metformin.Journal of Cancer · 2022Article
- Targeting Oxidative Phosphorylation-Proteasome Activity in Extracellular Detached Cells Promotes Anoikis and Inhibits Metastasis.Life (Basel, Switzerland) · 2021Article
- Metformin Downregulates PD-L1 Expression in Esophageal Squamous Cell Catrcinoma by Inhibiting IL-6 Signaling Pathway.Frontiers in oncology · 2021Article
- Adverse Effects of Metformin From Diabetes to COVID-19, Cancer, Neurodegenerative Diseases, and Aging: Is VDAC1 a Common Target?Frontiers in physiology · 2021Review
- Metformin regulation of progesterone receptor isoform-B expression in human endometrial cancer cells is glucose-dependent.Oncology letters · 2020Article
- Counteracting Chemoresistance with Metformin in Breast Cancers: Targeting Cancer Stem Cells.Cancers · 2020Review
- Metformin Derivative HL156A Reverses Multidrug Resistance by Inhibiting HOXC6/ERK1/2 Signaling in Multidrug-Resistant Human Cancer Cells.Pharmaceuticals (Basel, Switzerland) · 2020Article
- Metformin inhibits metastatic breast cancer progression and improves chemosensitivity by inducing vessel normalization via PDGF-B downregulation.Journal of experimental & clinical cancer research : CR · 2019Article
- PYK2 promotes HER2-positive breast cancer invasion.Journal of experimental & clinical cancer research : CR · 2019Article
- Metformin as an adjuvant in breast cancer treatment.SAGE open medicine · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Multiple drug resistant (MDR) malignancy remains a predictable and often terminal event in cancer therapy, and affects individuals with many cancer types, regardless of the stage at which they were originally diagnosed or the interval from last treatment. Protein biomarkers of MDR are not globally used for clinical decision-making, but include the overexpression of drug-efflux pumps (ABC transporter family) such as MDR-1 and BCRP, as well as HIF1α, a stress responsive transcription factor found elevated within many MDR tumors. Here, we present the important in vitro discovery that the development of MDR (in breast cancer cells) can be prevented, and that established MDR could be resensitized to therapy, by adjunct treatment with metformin. Metformin is prescribed globally to improve insulin sensitivity, including in those individuals with Type 2 Diabetes Mellitus (DM2). We demonstrate the effectiveness of metformin in resensitizing MDR breast cancer cell lines to their original treatment, and provide evidence that metformin may function through a mechanism involving post-translational histone modifications via an indirect histone deacetylase inhibitor (HDACi) activity. We find that metformin, at low physiological concentrations, reduces the expression of multiple classic protein markers of MDR in vitro and in preliminary in vivo models. Our demonstration that metformin can prevent MDR development and resensitize MDR cells to chemotherapy in vitro, provides important medical relevance towards metformin's potential clinical use against MDR 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.