ArticleCancer immunology, immunotherapy : CII2022
Metformin inhibits human non-small cell lung cancer by regulating AMPK-CEBPB-PDL1 signaling pathway.
Article in Cancer immunology, immunotherapy : CII, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 40 citations in OpenAlex.
- 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
- Targeting UXS1-Dependent Glucuronate Detoxification Potentiates Metformin's Anti-Tumor Efficacy in Lung Adenocarcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- CEBPB emerges as a key regulatory factor in human cancers through diverse molecular mechanisms and clinical implications.Discover oncology · 2025Review
- Are metformin-based combination approaches beneficial for non-small cell lung cancer: evidence from experimental and clinical studies.Military Medical Research · 2025Review
- Article
- The complex interplay of TROP2 and PD-L1 in immune regulation and drug resistance in lung cancer.American journal of cancer research · 2025Article
- N-terminal acetylation of transcription factor LIP induces immune therapy resistance via suppression of PD-L1 expression in non-small cell lung cancer.Journal for immunotherapy of cancer · 2024Article
- Cardiomyocyte-specific knockout of ADAM17 alleviates doxorubicin-induced cardiomyopathy via inhibiting TNFα-TRAF3-TAK1-MAPK axis.Signal transduction and targeted therapy · 2024Article
- Anticarcinogenic Effects of Gold Nanoparticles and Metformin Against MCF-7 and A549 Cells.Biological trace element research · 2024Article
- Metformin is a potential therapeutic for COVID-19/LUAD by regulating glucose metabolism.Scientific reports · 2024Article
- IL6-STAT3-C/EBPβ-IL6 positive feedback loop in tumor-associated macrophages promotes the EMT and metastasis of lung adenocarcinoma.Journal of experimental & clinical cancer research : CR · 2024Article
- Impact of Radiation Therapy on Serum Humanin and MOTS-c Levels in Patients with Lung or Breast Cancer.Current radiopharmaceuticals · 2024Observational
- Novel Adiponectin Receptor Agonist Inhibits Cholangiocarcinoma via Adenosine Monophosphate-activated Protein Kinase.Current medicinal chemistry · 2024Article
- Exploiting the Achilles' heel of cancer: disrupting glutamine metabolism for effective cancer treatment.Frontiers in pharmacology · 2024Review
- Sakurasosaponin inhibits lung cancer cell proliferation by inducing autophagy via AMPK activation.Oncology letters · 2023Article
- LINC01133 can induce acquired ferroptosis resistance by enhancing the FSP1 mRNA stability through forming the LINC01133-FUS-FSP1 complex.Cell death & disease · 2023Article
- [Research Progress on the Combination Therapy of EGFR-TKIs and Metformin in Acquired Resistance to EGFR-TKIs in Non-small Cell Lung Cancer].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2023Article
- Identification of TCR rearrangements specific for genetic alterations in EGFR-mutated non-small cell lung cancer: results from the ADJUVANT-CTONG1104 trial.Cancer immunology, immunotherapy : CII · 2023Article
- DMU-212 against EGFR-mutant non-small cell lung cancer via AMPK/PI3K/Erk signaling pathway.Heliyon · 2023Article
- Efficacy of metformin adjunctive therapy as the treatment for non-diabetic patients with advanced non-small cell lung cancer: A Systematic review and Meta-analysis.Journal of research in medical sciences : the official journal of Isfahan University of Medical Sciences · 2023Review
Corrections and comments
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
Abstract
Metformin has been found to have inhibitory effects on a variety of tumors. However, its effects on non-small cell lung cancer (NSCLC) remain unclear. We demonstrated that metformin could inhibit the proliferation of A549 and H1299 cells. RNA transcriptome sequencing revealed that PDL1 was significantly downregulated in both cell types following treatment with metformin (P < 0.001). Jaspar analysis and chromatin immunoprecipitation showed that CEBPB could directly bind the promoter region of PDL1. Western blotting showed that protein expression of the isoforms CEBPB-LAP*, CEBPB-LAP, and CEBPB-LIP was significantly upregulated and the LIP/LAP ratio was increased. Gene chip analysis showed that PDL1 was significantly upregulated in A549-CEBPB-LAP cells and significantly downregulated in A549-CEBPB-LIP cells (P < 0.05) compared with CEBPB-NC cells. Dual-luciferase reporter gene assay showed that CEBPB-LAP overexpression could promote transcription of PDL1 and CEBPB-LIP overexpression could inhibit the process. Functional assays showed that the changes in CEBPB isoforms affected the function of NSCLC cells. Western blotting showed that metformin could regulate the function of NSCLC cells via AMPK-CEBPB-PDL1 signaling. Animal experiments showed that tumor growth was significantly inhibited by metformin, and atezolizumab and metformin had a synergistic effect on tumor growth. A total of 1247 patients were retrospectively analyzed, including 166 and 1081 patients in metformin and control groups, respectively. The positive rate of PDL1 was lower than that of the control group (HR = 0.338, 95% CI = 0.235-0.487; P < 0.001). In conclusion, metformin inhibited the proliferation of NSCLC cells and played an anti-tumor role in an AMPK-CEBPB-PDL1 signaling-dependent manner.
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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.