ArticleOncotarget2016
Metformin increases antitumor activity of MEK inhibitors through GLI1 downregulation in LKB1 positive human NSCLC cancer cells.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
50 citing papers in PubMed, 2 syntheses or guidelines pooled it, 68 citations in OpenAlex.
- The Impact of Metformin on Vitamin B12 Levels in Children and Adolescents: A Systematic Review and Single-Arm Meta-Analysis.Endocrinology, diabetes & metabolism · 2026Pooled it
- Impact of Metformin on Cancer Biomarkers in Non-Diabetic Cancer Patients: A Systematic Review and Meta-Analysis of Clinical Trials.Current oncology (Toronto, Ont.) · 2021Pooled it
- Trial
- Metformin potentiates arsenic disulfide in diffuse large B-cell lymphoma: modulation of BAX/BCL-2 apoptotic pathway and hedgehog pathway.Frontiers in oncology · 2026Article
- A novel effect of bevacizumab in reducing characteristic pigmentation in Peutz-Jeghers syndrome: a case report and literature review.Frontiers in oncology · 2025Article
- Metformin and its Nanoformulations in Cancer Prevention and Therapy.Current pharmaceutical design · 2025Review
- Optimized Nanostructured Lipid Carriers for Metformin: Enhanced Anti-Inflammatory Activity and Protection Against Type 2 Diabetes-Induced Organ Damage.International journal of nanomedicine · 2025Article
- Advances in the Insulin-Heart Axis: Current Therapies and Future Directions.International journal of molecular sciences · 2024Review
- Therapeutic implications of the metabolic changes associated with BRAF inhibition in melanoma.Cancer treatment reviews · 2024Review
- Pharmacological characterization of the antidiabetic drug metformin in atherosclerosis inhibition: A comprehensive insight.Immunity, inflammation and disease · 2024Review
- NCI 159456 PERK Inhibitor as a Targeted Therapy for Lung Cancer: An In Vitro Study.Biomedicines · 2024Article
- The anti-inflammatory effect of metformin: The molecular targets.Genes to cells : devoted to molecular & cellular mechanisms · 2024Review
- A Novel Combination of Sotorasib and Metformin Enhances Cytotoxicity and Apoptosis in KRAS-Mutated Non-Small Cell Lung Cancer Cell Lines through MAPK and P70S6K Inhibition.International journal of molecular sciences · 2023Article
- Serum Concentrations and Dietary Intake of Vitamin BInternational journal of molecular sciences · 2023Article
- Hypertension, type 2 diabetes, obesity, and p53 mutations negatively correlate with metastatic colorectal cancer patients' survival.Frontiers in medicine · 2023Article
- Research progress on the therapeutic effect and mechanism of metformin for lung cancer (Review).Oncology reports · 2023Review
- Metformin use and the risk of total knee replacement among diabetic patients: a propensity-score-matched retrospective cohort study.Scientific reports · 2022Article
- Metformin Intervention-A Panacea for Cancer Treatment?Cancers · 2022Review
- The Relationship Between Diabetes Mellitus and Cancers and Its Underlying Mechanisms.Frontiers in endocrinology · 2022Review
- Integrated or Independent Actions of Metformin in Target Tissues Underlying Its Current Use and New Possible Applications in the Endocrine and Metabolic Disorder Area.International journal of molecular sciences · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeMetformin, widely used as antidiabetic drug, showed antitumoral effects expecially in combination with chemotherapy. Our group recently has demonstrated that metformin and gefitinib are synergistic in LKB1-wild-type NSCLC cells. In these models, metformin as single agent induced an activation and phosphorylation of mitogen-activated-protein-kinase (MAPK) through an increased C-RAF/B-RAF heterodimerization. EXPERIMENTAL
designSince single agent metformin enhances proliferating signals through the RAS/RAF/MAPK pathway, and several MEK inhibitors (MEK-I) demonstrated clinical efficacy in combination with other agents in NSCLC, we tested the effects of metformin plus MEK-I (selumetinib or pimasertib) on proliferation, invasiveness, migration abilities in vitro and in vivo in LKB1 positive NSCLC models harboring KRAS wild type and mutated gene.
resultsThe combination of metformin with MEK-I showed a strong anti-proliferative and proapoptotic effect in Calu-3, H1299, H358 and H1975 human NSCLC cell lines, independently from the KRAS mutational status. The combination reduced the metastatic behaviour of NSCLC cells, via a downregulation of GLI1 trascritional activity, thus affecting the transition from an epithelial to a mesenchymal phenotype. Metformin and MEK-Is combinations also decreased the production and activity of MMP-2 and MMP-9 by reducing the NF-jB (p65) binding to MMP-2 and MMP-9 promoters.
conclusionsMetformin potentiates the antitumor activity of MEK-Is in human LKB1-wild-type NSCLC cell lines, independently from the KRAS mutational status, through GLI1 downregulation and by reducing the NF-jB (p65)-mediated transcription of MMP-2 and MMP-9.
Indexed as
Identifiers
What OpenQuestion holds
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.