ArticleBritish journal of cancer2013
Metformin inhibits growth and enhances radiation response of non-small cell lung cancer (NSCLC) through ATM and AMPK.
Article in British journal of cancer, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 153 papers, 3 of them syntheses that pooled it.
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Who cites it
153 citing papers in PubMed, 3 syntheses or guidelines pooled it, 268 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
- Top 100 most-cited articles on apoptosis of non-small cell lung cancer over the past two decades: a bibliometrics analysis.Frontiers in immunology · 2024Pooled it
- Metformin therapy associated with survival benefit in lung cancer patients with diabetes.Oncotarget · 2016 · on this mapPooled it
- Growth differentiation factor 15 (GDF15) predicts relapse free and overall survival in unresected locally advanced non-small cell lung cancer treated with chemoradiotherapy.Radiation oncology (London, England) · 2024Trial
- Metformin in Conjunction With Stereotactic Radiotherapy for Early-stage Non-small Cell Lung Cancer: Long-term Results of a Prospective Phase II Clinical Trial.Anticancer research · 2024Trial
- STAT5A-RNF8 signaling regulates homologous recombination repair and cisplatin responsiveness in cervical cancer.Neoplasia (New York, N.Y.) · 2026Article
- Multi-Target Antitumor Effects of Natural Products and Approved Drug Repurposing in Non-Small Cell Lung Cancer: Advances in Mechanisms, Combination Regimens, Delivery System Optimization, and Clinical Challenges.International journal of molecular sciences · 2026Review
- HER2-specific synthetic antigen receptor T cell therapy synergizes with radiotherapy to provide improved antitumor efficacy in non-small cell lung cancer.Journal of leukocyte biology · 2026Article
- Investigating the causal link between metformin and lung cancer risk: a two-sample mendelian randomization analysis.BMC cancer · 2026Article
- Metformin Inhibits Inflammation by Targeting the NLRP3 Inflammasome: Linking NF-κB/NEK7/AMPK Signaling to Mitochondrial Function.Journal of inflammation research · 2026Review
- p53 Orchestrates the Immunogenic-Tolerogenic Pyroptosis Switch in Non-Small Cell Lung Cancer: A Systems Biology Approach.Computational and structural biotechnology journal · 2026Article
- Altered Pulmonary Glucose Transport Is Restored by Metformin Treatment in an Obese Type 2 Diabetic Animal Model.Metabolites · 2025Article
- Metabolic stress-mediated cell death and autophagy in human lung cancer cells.The Journal of pharmacology and experimental therapeutics · 2025Article
- Radiosensitizing Effects of Metformin on Ionizing Irradiation: An Overview of Animal and Clinical Studies.Current drug research reviews · 2025Review
- Radiotherapy-induced alterations in tumor microenvironment: metabolism and immunity.Frontiers in cell and developmental biology · 2025Review
- Metformin and its Nanoformulations in Cancer Prevention and Therapy.Current pharmaceutical design · 2025Review
- Enhanced Anticancer Activity of 7MeERT over Ertredin: A Comparative Study on Cancer Cell Proliferation and NDUFA12 Binding.Biomolecules · 2024Article
- MicroRNAs targeted mTOR as therapeutic agents to improve radiotherapy outcome.Cancer cell international · 2024Review
- Metformin: A Dual-Role Player in Cancer Treatment and Prevention.International journal of molecular sciences · 2024Review
- AMPK Alchemy: Therapeutic Potentials in Allergy, Aging, and Cancer.Biomolecules & therapeutics · 2024Review
93 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundWe examined the potential of metformin (MET) to enhance non-small cell lung cancer (NSCLC) responses to ionising radiation (IR).
methodsHuman NSCLC cells, mouse embryonic fibroblasts from wild-type and AMP-activated kinase (AMPK) α1/2-subunit(-/-) embryos (AMPKα1/2(-/-)-MEFs) and NSCLC tumours grafted into Balb/c-nude mice were treated with IR and MET and subjected to proliferation, clonogenic, immunoblotting, cell cycle and apoptosis assays and immunohistochemistry (IHC).
resultsMetformin (2.5 μM-5 mM) inhibited proliferation and radio-sensitised NSCLC cells. Metformin (i) activated the ataxia telengiectasia-mutated (ATM)-AMPK-p53/p21(cip1) and inhibited the Akt-mammalian target of rapamycin (mTOR)-eIF4E-binding protein 1 (4EBP1) pathways, (ii) induced G1 cycle arrest and (iii) enhanced apoptosis. ATM inhibition blocked MET and IR activation of AMPK. Non-small cell lung cancer cells with inhibited AMPK and AMPKα1/2(-/-)-MEFs were resistant to the antiproliferative effects of MET and IR. Metformin or IR inhibited xenograft growth and combined treatment enhanced it further than each treatment alone. Ionising radiation and MET induced (i) sustained activation of ATM-AMPK-p53/p21(cip1) and inhibition of Akt-mTOR-4EBP1 pathways in tumours, (ii) reduced expression of angiogenesis and (iii) enhanced expression of apoptosis markers.
conclusionClinically achievable MET doses inhibit NSCLC cell and tumour growth and sensitise them to IR. Metformin and IR mediate their action through an ATM-AMPK-dependent pathway. Our results suggest that MET can be a clinically useful adjunct to radiotherapy in NSCLC.
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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.