ArticleInternational journal of molecular sciences2018
Metformin Inhibits Migration and Invasion by Suppressing ROS Production and COX2 Expression in MDA-MB-231 Breast Cancer Cells.
Article in International journal of molecular sciences, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
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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.
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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
28 citing papers in PubMed, 53 citations in OpenAlex.
- Metformin as an Adjunct in Periodontal Therapy: Mechanistic Insights, Research Evidence and Current Challenges.Therapeutic innovation & regulatory science · 2026Review
- Safety and efficacy of chemoprevention for familial adenomatous polyposis: a systematic review and meta-analysis.Annals of coloproctology · 2026Review
- Optimizing Silver Nanoparticle Properties: Synergistic Effects of Green Synthesis and Calcination on Crystallinity, Stability, and Bioactivity.Applied biochemistry and biotechnology · 2026Article
- Mitochondrial Reactive Oxygen Species (mROS) Generation and Cancer:International journal of nanomedicine · 2025Review
- Article
- Review
- Adipose Tissue in Breast Cancer Microphysiological Models to Capture Human Diversity in Preclinical Models.International journal of molecular sciences · 2024Review
- Article
- Intermediate Filaments in Breast Cancer Progression, and Potential Biomarker for Cancer Therapy: A Narrative Review.Breast cancer (Dove Medical Press) · 2024Review
- Revealing the role of metformin in gastric intestinal metaplasia treatment.Frontiers in pharmacology · 2024Article
- Combination of metformin/efavirenz/fluoxetine exhibits profound anticancer activity via a cancer cell-specific ROS amplification.Cancer biology & therapy · 2023Article
- The great obstetrical syndromes and the placenta.BJOG : an international journal of obstetrics and gynaecology · 2023Review
- Dihydrotanshinone Triggers Porimin-Dependent Oncosis by ROS-Mediated Mitochondrial Dysfunction in Non-Small-Cell Lung Cancer.International journal of molecular sciences · 2023Article
- Marked paper: Type 2 diabetes mellitus indicates increased postoperative complications and poor prognosis in colorectal cancer patients receiving curative surgery.Frontiers in oncology · 2023Article
- The Role and Mechanism of Metformin in Inflammatory Diseases.Journal of inflammation research · 2023Review
- The 3D in vivo chorioallantoic membrane model and its role in breast cancer research.Journal of cancer research and clinical oncology · 2022Review
- The crosstalk within the breast tumor microenvironment in type II diabetes: Implications for cancer disparities.Frontiers in endocrinology · 2022Review
- Metformin for Cardiovascular Protection, Inflammatory Bowel Disease, Osteoporosis, Periodontitis, Polycystic Ovarian Syndrome, Neurodegeneration, Cancer, Inflammation and Senescence: What Is Next?ACS pharmacology & translational science · 2021Review
- Mitochondrial Dynamics, ROS, and Cell Signaling: A Blended Overview.Life (Basel, Switzerland) · 2021Review
- Towards an Integral Therapeutic Protocol for Breast Cancer Based upon the New HInternational journal of molecular sciences · 2020Review
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
backgroundSeveral mechanisms of action have been proposed to explain the apparent antineoplastic functions of metformin, many of which are observed at high concentrations that may not be reflective of achievable tissue concentrations. We propose that metformin at low concentrations functions to inhibit ROS production and inflammatory signaling in breast cancer, thereby reducing metastasis.
methodsUsing the highly invasive MDA-MB-231 breast carcinoma model, we ascertained the impact of metformin on cell viability by DNA content analysis and fluorescent dye exclusion. Migration and invasion assays were performed using a modified Boyden chamber assay and metastasis was ascertained using the chorioallantoic membrane (CAM) assay. PGE2 production was measured by Enzyme-Linked Immunosorbent Assay (ELISA). COX2 and ICAM1 levels were determined by flow cytometry immunoassay.
resultsMetformin acutely decreased cell viability and caused G2 cell cycle arrest only at high concentrations (10 mM). At 100 µM, however, metformin reduced ICAM1 and COX2 expression, as well as reduced PGE2 production and endogenous mitochondrial ROS production while failing to significantly impact cell viability. Consequently, metformin inhibited migration, invasion in vitro and PGE2-dependent metastasis in CAM assays.
conclusionAt pharmacologically achievable concentrations, metformin does not drastically impact cell viability, but inhibits inflammatory signaling and metastatic progression in breast cancer cells.
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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.