ArticleInternational journal of oncology2018
Metformin inhibits ovarian cancer via decreasing H3K27 trimethylation.
Article in International journal of oncology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 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
47 citing papers in PubMed, 1 synthesis or guideline pooled it, 66 citations in OpenAlex.
- Targeting epigenetics and non-coding RNAs in atherosclerosis: from mechanisms to therapeutics.Pharmacology & therapeutics · 2019Pooled it
- Phase II clinical trial of metformin as a cancer stem cell-targeting agent in ovarian cancer.JCI insight · 2020Trial
- Overcoming Therapy Resistance in Ovarian Cancer: From Molecular Mechanisms to Emerging Therapeutic Strategies.Cancers · 2026Review
- Article
- Metformin-A Type 2 Diabetes Mellitus Drug-And Ovarian Cancer: Anticancer Mechanisms and Therapeutic Implications.Biomolecules · 2026Review
- The role of epigenetics in cancer: From pathways to the clinic.Journal of family medicine and primary care · 2025Review
- The Anti-Aging Mechanism of Metformin: From Molecular Insights to Clinical Applications.Molecules (Basel, Switzerland) · 2025Review
- Maternal Metformin Administration During the Pre-Gestation Period Improves Transient Cerebral Ischemia Injury in Male Offspring Rats.Advanced pharmaceutical bulletin · 2024Article
- Anti-Diabetic Therapies and Cancer: From Bench to Bedside.Biomolecules · 2024Review
- Dietary phytosterols induce infertility in female mice via epigenomic modulations.Communications biology · 2024Article
- Article
- Metformin induces tumor immunogenic cell death in ovarian cancer by activating AMPK pathway.Translational oncology · 2024Article
- Impacts of Dietary Standardized Ileal Digestible Lysine to Net Energy Ratio on Lipid Metabolism in Finishing Pigs Fed High-Wheat Diets.Animals : an open access journal from MDPI · 2024Article
- Exosomes biogenesis was increased in metformin-treated human ovary cancer cells; possibly to mediate resistance.Cancer cell international · 2024Article
- Chromatin modifiers in human disease: from functional roles to regulatory mechanisms.Molecular biomedicine · 2024Review
- Article
- Bridging the gap: exploring the causal relationship between metformin and tumors.Frontiers in genetics · 2024Article
- Current status and frontier tracking of clinical trials on Metformin for cancer treatment.Journal of cancer research and clinical oncology · 2023Review
- Metformin regulates expression of DNA methyltransferases through the miR-148/-152 family in non-small lung cancer cells.Clinical epigenetics · 2023Article
- The Epigenetic Landscape of Meningiomas.Advances in experimental medicine and biology · 2023Article
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 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Metformin has been used for the treatment of type II diabetes mellitus for decades. Recently, used of metformin in the therapy of diverse human cancer types has received widespread attention, while the underlying mechanisms have been not fully elucidated. In the current study, 5-ethynyl-20-deoxyuridine assay to detect cell proliferation, flow cytometry to detect apoptosis, scratch wound healing and Transwell migration assay to detect cell migration capacity. The current study reported that metformin inhibited cell proliferation and migration, and promoted apoptosis in ovarian cancer cells, particularly under normoglycemic conditions in vitro. Metformin treatment significantly promoted the phosphorylation of AMP-activated protein kinase (AMPK), and reduced histone H3 lysine 27 trimethylation (H3K27me3) and polycomb repressor complex 2 (PRC2) levels. Additionally, overexpression of EZH2 to increase H3K27me3 abrogated the effect of metformin on the cell proliferation, migration and apoptosis in SKOV3 and ES2 cells. Similar to metformin, another AMPK agonist, 2-deoxy-D-glucose, reduced the H3K27me3 level and PRC2 expression. In cells pretreated with Compound C, an AMPK inhibitor, metformin was not able to induce AMPK phosphorylation or reduce H3K27me3. Metformin-mediated AMPK activation and H3K27me3 inhibition were more robust in cells exposed to low glucose (5.5 mM) compared with those exposed to high glucose (25 mM). These findings implicate H3K27me3 repression mediated by AMPK phosphorylation in the antitumor effect of metformin in ovarian cancer, indicating that metformin alters epigenetic modifications by targeting PRC2 and supports the use of metformin in treatment of patients with epithelial ovarian cancer without diabetes.
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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.