ArticleCancer prevention research (Philadelphia, Pa.)2013
Inhibition of lung tumorigenesis by metformin is associated with decreased plasma IGF-I and diminished receptor tyrosine kinase signaling.
Article in Cancer prevention research (Philadelphia, Pa.), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 2 of them syntheses that pooled it.
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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
55 citing papers in PubMed, 2 syntheses or guidelines pooled it, 84 citations in OpenAlex.
- Metformin therapy associated with survival benefit in lung cancer patients with diabetes.Oncotarget · 2016 · on this mapPooled it
- Conventional hypoglycaemic agents and the risk of lung cancer in patients with diabetes: a meta-analysis.PloS one · 2014 · on this mapPooled it
- Bioactivity and prostate tissue distribution of metformin in a preprostatectomy prostate cancer cohort.European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP) · 2018Trial
- A Randomized Phase II Study of Metformin plus Paclitaxel/Carboplatin/Bevacizumab in Patients with Chemotherapy-Naïve Advanced or Metastatic Nonsquamous Non-Small Cell Lung Cancer.The oncologist · 2018Trial
- The dual facets of MiRNA in modulating NF-κB in breast cancer.Cancer cell international · 2025Review
- Metformin protects against cyclophosphamide-induced ovarian fibrosis by MIF/CD74-mediated macrophage polarization.Journal of translational medicine · 2025Article
- Metformin and its Nanoformulations in Cancer Prevention and Therapy.Current pharmaceutical design · 2025Review
- Genistein as a Chemo-modulatory Agent: Exploring its Potential in Chemosensitization and Combinatorial Therapeutic Strategies for Cancer Treatment.Current topics in medicinal chemistry · 2025Review
- Delineating the role of nuclear receptors in colorectal cancer, a focused review.Discover oncology · 2024Review
- Harnessing Sulforaphane Potential as a Chemosensitizing Agent: A Comprehensive Review.Cancers · 2024Review
- Natural compounds targeting nuclear receptors for effective cancer therapy.Cancer metastasis reviews · 2023Review
- Discovering Biological Mechanisms of Exceptional Human Health Span and Life Span.Cold Spring Harbor perspectives in medicine · 2023Review
- Metformin: update on mechanisms of action and repurposing potential.Nature reviews. Endocrinology · 2023Review
- Curcumin Formulations for Better Bioavailability: What We Learned from Clinical Trials Thus Far?ACS omega · 2023Review
- Metformin in therapeutic applications in human diseases: its mechanism of action and clinical study.Molecular biomedicine · 2022Review
- Unraveling the Potential Role of NEDD4-like E3 Ligases in Cancer.International journal of molecular sciences · 2022Review
- Metformin counteracts stimulatory effects induced by insulin in primary breast cancer cells.Journal of translational medicine · 2022Article
- Metformin and arsenic trioxide synergize to trigger Parkin/pink1-dependent mitophagic cell death in human cervical cancer HeLa cells.Journal of Cancer · 2021Article
- The promising potential of piperlongumine as an emerging therapeutics for cancer.Exploration of targeted anti-tumor therapy · 2021Review
- Metformin induces apoptosis and inhibits migration by activating the AMPK/p53 axis and suppressing PI3K/AKT signaling in human cervical cancer cells.Molecular medicine reports · 2021Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Metformin is the most commonly prescribed drug for type II diabetes and is associated with decreased cancer risk. Previously, we showed that metformin prevented tobacco carcinogen (NNK)-induced lung tumorigenesis in a non-diabetic mouse model, which was associated with decreased IGF-I/insulin receptor signaling but not activation of AMPK in lung tissues, as well as decreased circulating levels of IGF-I and insulin. Here, we used liver IGF-I-deficient (LID) mice to determine the importance of IGF-I in NNK-induced lung tumorigenesis and chemoprevention by metformin. LID mice had decreased lung tumor multiplicity and burden compared with wild-type (WT) mice. Metformin further decreased lung tumorigenesis in LID mice without affecting IGF-I levels, suggesting that metformin can act through IGF-I-independent mechanisms. In lung tissues, metformin decreased phosphorylation of multiple receptor tyrosine kinases (RTK) as well as levels of GTP-bound Ras independently of AMPK. Metformin also diminished plasma levels of several cognate ligands for these RTKs. Tissue distribution studies using [(14)C]-metformin showed that uptake of metformin was high in liver but four-fold lower in lungs, suggesting that the suppression of RTK activation by metformin occurs predominantly via systemic, indirect effects. Systemic inhibition of circulating growth factors and local RTK signaling are new AMPK-independent mechanisms of action of metformin that could underlie its ability to prevent tobacco carcinogen-induced lung tumorigenesis.
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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.