ArticlePloS one2013
Low concentrations of metformin selectively inhibit CD133⁺ cell proliferation in pancreatic cancer and have anticancer action.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers, 2 of them syntheses 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
66 citing papers in PubMed, 2 syntheses or guidelines pooled it, 107 citations in OpenAlex.
- Do We Have Enough Evidence That Metformin Is Superior to Other Antidiabetic Drugs in Pancreatic Cancer Risk Reduction?International journal of molecular sciences · 2026Pooled it
- Effect of Metformin and Statin Use on Survival in Pancreatic Cancer Patients: a Systematic Literature Review and Meta-analysis.Current medicinal chemistry · 2018Pooled it
- Metformin as a Multifaceted Therapeutic Agent for Gastrointestinal Diseases: Mechanisms, Clinical Efficacy, and Future Directions.Pharmacology research & perspectives · 2026Review
- Research Progress on the Molecular Mechanism of Metformin Regulating AMPK Signaling Pathway in Inhibiting Liver Cancer.OncoTargets and therapy · 2026Review
- Prolonged Low-Dose Administration of FDA-Approved Drugs for Non-Cancer Conditions: A Review of Potential Targets in Cancer Cells.International journal of molecular sciences · 2025Review
- Dual delivery of metformin and Y15 from a PLGA scaffold for the treatment of platinum-resistant ovarian cancer.Future medicinal chemistry · 2025Article
- The intricate interplay between cancer stem cells and cell-of-origin of cancer: implications for therapeutic strategies.Frontiers in oncology · 2024Review
- Unmasking the Deceptive Nature of Cancer Stem Cells: The Role of CD133 in Revealing Their Secrets.International journal of molecular sciences · 2023Review
- Anti-cancer effects of metformin in a 3D co-culture model of pancreatic ductal adenocarcinoma.American journal of cancer research · 2023Article
- Research progress in the establishment of pancreatic cancer models and preclinical applications.Cancer innovation · 2022Review
- Small molecule QF84139 ameliorates cardiac hypertrophy via activating the AMPK signaling pathway.Acta pharmacologica Sinica · 2022Article
- Knockdown ofBiomolecules & therapeutics · 2021Article
- Green Synthesized Honokiol Transfersomes Relieve the Immunosuppressive and Stem-Like Cell Characteristics of the Aggressive B16F10 Melanoma.International journal of nanomedicine · 2021Article
- Cohort Study of Antihyperglycemic Medication and Pancreatic Cancer Patients Survival.International journal of environmental research and public health · 2020Article
- Overexpression of YBX1 Promotes Pancreatic Ductal Adenocarcinoma Growth via the GSK3B/Cyclin D1/Cyclin E1 Pathway.Molecular therapy oncolytics · 2020Article
- Metformin activates AMPK/SIRT1/NF-κB pathway and induces mitochondrial dysfunction to drive caspase3/GSDME-mediated cancer cell pyroptosis.Cell cycle (Georgetown, Tex.) · 2020Article
- Selective phytochemicals targeting pancreatic stellate cells as new anti-fibrotic agents for chronic pancreatitis and pancreatic cancer.Acta pharmaceutica Sinica. B · 2020Review
- Metformin Inhibited Proliferation and Metastasis of Colorectal Cancer and presented a Synergistic Effect on 5-FU.BioMed research international · 2020Article
- The Role of Stellate Cells in Pancreatic Ductal Adenocarcinoma: Targeting Perspectives.Frontiers in oncology · 2020Review
- Clinical Characteristics and Prevalence of Comorbidities according to Metformin Use in Korean Patients with Type 2 Diabetes.International journal of endocrinology · 2020Article
6 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
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pancreatic cancer is the fourth leading cause of cancer related deaths in the United States. The prognosis remains dismal with little advance in treatment. Metformin is a drug widely used for the treatment of type II diabetes. Recent epidemiologic data revealed that oral administration of metformin is associated with a reduced risk of pancreatic cancer, suggesting its potential as a novel drug for this disease. Many studies have demonstrated the in vitro anticancer action of metformin, but the typically used concentrations were much higher than the in vivo plasma and tissue concentrations achieved with recommended therapeutic doses of metformin, and low concentrations of metformin had little effect on the proliferation of pancreatic cancer cells. We examined the effect of low concentrations of metformin on different subpopulations of pancreatic cancer cells and found that these selectively inhibited the proliferation of CD133⁺ but not CD24⁺CD44⁺ESA⁺ cells. We also examined the effect of low concentrations of metformin on cell invasion and in vivo tumor formation, demonstrating in vitro and in vivo anticancer action. Metformin was associated with a reduction of phospho-Erk and phospho-mTOR independent of Akt and AMPK phosphorylation. CD133⁺ pancreatic cancer cells are considered to be cancer stem cells that contribute to recurrence, metastasis and resistance to adjuvant therapies in pancreatic cancer. Our results provide a basis for combination of metformin with current therapies to improve the prognosis of this disease.
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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.