ArticleOncotarget2016
Metformin restores crizotinib sensitivity in crizotinib-resistant human lung cancer cells through inhibition of IGF1-R signaling pathway.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 45 citations in OpenAlex.
- Three decades of anaplastic lymphoma kinase: from physiological roles to cancer and immune evasion.Cancer metastasis reviews · 2026Review
- The therapeutic value of antidiabetic drugs in lung cancer treatment: from clinical evidence to possible mechanisms.Frontiers in immunology · 2026Review
- Anti-EGFR therapy can overcome acquired resistance to the third-generation ALK-tyrosine kinase inhibitor lorlatinib mediated by activation of EGFR.Acta pharmacologica Sinica · 2025Article
- Metformin and glioma: Targeting metabolic dysregulation for enhanced therapeutic outcomes.Translational oncology · 2025Review
- Mechanisms of Resistance to ALK Inhibitors and Corresponding Treatment Strategies in Lung Cancer.International journal of general medicine · 2025Review
- Metformin: A Dual-Role Player in Cancer Treatment and Prevention.International journal of molecular sciences · 2024Review
- Research progress on the therapeutic effect and mechanism of metformin for lung cancer (Review).Oncology reports · 2023Review
- Will We Unlock the Benefit of Metformin for Patients with Lung Cancer? Lessons from Current Evidence and New Hypotheses.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Impact of metformin on tyrosine kinase inhibitor response in chronic myeloid leukemia.Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners · 2022Observational
- An insight into lung cancer: a comprehensive review exploring ALK TKI and mechanisms of resistance.Bosnian journal of basic medical sciences · 2022Review
- Hexokinases II-mediated glycolysis governs susceptibility to crizotinib in ALK-positive non-small cell lung cancer.Thoracic cancer · 2021Article
- Clinical Predictors of Prolonged Hospital Stay in Patients with Myasthenia Gravis: A Study Using Machine Learning Algorithms.Journal of clinical medicine · 2021Article
- Metformin impairs cisplatin resistance effects in A549 lung cancer cells through mTOR signaling and other metabolic pathways.International journal of oncology · 2021Article
- Relationship between long non-coding RNA PCAT-1 expression and gefitinib resistance in non-small-cell lung cancer cells.Respiratory research · 2021Article
- Molecular mechanisms underlining the role of metformin as a therapeutic agent in lung cancer.Cellular oncology (Dordrecht, Netherlands) · 2021Review
- Activation of IGF-1R pathway and NPM-ALK G1269A mutation confer resistance to crizotinib treatment in NPM-ALK positive lymphoma.Investigational new drugs · 2020Article
- [Research Advance in Anti-lung Cancer Mechanism of Metformin].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2020Review
- Metformin reduces HGF-induced resistance to alectinib via the inhibition of Gab1.Cell death & disease · 2020Article
- Metastasis manners and the underlying mechanisms of ALK and ROS1 rearrangement lung cancer and current possible therapeutic strategies.RSC advances · 2019Review
- Metformin and tenovin-6 synergistically induces apoptosis through LKB1-independent SIRT1 down-regulation in non-small cell lung cancer cells.Journal of cellular and molecular medicine · 2019Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimDespite the impressive efficacy of crizotinib for the treatment of ALK-positive non-small cell lung cancer, patients invariably develop therapeutic resistance. Suppression of the IGF-1R signaling pathway may abrogate this acquired mechanism of drug resistance to crizotinib. Metformin, a widely used antidiabetic agent, may reverse crizotinib resistance through inhibition of IGF-1R signaling.
resultsThe present study revealed that metformin effectively increased the sensitivity of both crizotinib-sensitive and -resistant non-small cell lung cancer cells to crizotinib, as evidenced by decreased proliferation and invasion and enhanced apoptosis. Metformin reduced IGF-1R signaling activation in crizotinib-resistant cells. Furthermore, the addition of IGF-1 to crizotinib-sensitive H2228 cells induced crizotinib resistance, which was overcome by metformin. EXPERIMENTAL
designThe effects of metformin to reverse crizotinib resistance were examined in vitro by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT), invasion assay, ki67 incorporation assay, flow cytometry analysis, Western blot analysis, and colony-forming assay.
conclusionsMetformin may be used in combination with crizotinib in ALK+ NSCLC patients to overcome crizotinib resistance and prolong survival.
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