ArticlePharmaceuticals (Basel, Switzerland)2022
Metformin Enhances TKI-Afatinib Cytotoxic Effect, Causing Downregulation of Glycolysis, Epithelial-Mesenchymal Transition, and EGFR-Signaling Pathway Activation in Lung Cancer Cells.
Article in Pharmaceuticals (Basel, Switzerland), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 15 citations in OpenAlex.
- Enhancing Curcumin Performance via PVP K30 Solid Dispersion: Synergistic Potential in Combination with Conventional Chemotherapeutic Agents in NSCLC Cells.AAPS PharmSciTech · 2026Article
- Investigating the causal link between metformin and lung cancer risk: a two-sample mendelian randomization analysis.BMC cancer · 2026Article
- Targeted metabolism creates possibilities for lung cancer treatment in the precision tumor era.Respiratory research · 2026Review
- Identification of a Lactate Accumulation Model to Explain the Heterogeneity in Prognosis, Immune Landscape, and Tumor Environment for HNSCC patients.Journal of Cancer · 2025Article
- Multimodal omics analysis of the EGFR signaling pathway in non-small cell lung cancer and emerging therapeutic strategies.Oncology research · 2025Review
- Astragalus Polysaccharides and Metformin May Have Synergistic Effects on the Apoptosis and Ferroptosis of Lung Adenocarcinoma A549 Cells.Current issues in molecular biology · 2024Article
- Advances in Non-Small Cell Lung Cancer (NSCLC) Treatment-A Paradigm Shift in Oncology.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Structure-activity relationships study ofFuture medicinal chemistry · 2024Article
- [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
- Article
- 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
- Will We Unlock the Benefit of Metformin for Patients with Lung Cancer? Lessons from Current Evidence and New Hypotheses.Pharmaceuticals (Basel, Switzerland) · 2022Review
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Authors and funding
9 authors at 5 institutions in 3 countries.
Funding
Abstract
The combination of metformin and TKIs for non-small cell lung cancer has been proposed as a strategy to overcome resistance of neoplastic cells induced by several molecular mechanisms. This study sought to investigate the effects of a second generation TKI afatinib, metformin, or their combination on three adenocarcinoma lung cancer cell lines with different EGFRmutation status. A549, H1975, and HCC827 cell lines were treated with afatinib, metformin, and their combination for 72 h. Afterwards, several parameters were assessed including cytotoxicity, interactions, apoptosis, and EGFR protein levels at the cell membrane and several glycolytic, oxidative phosphorylation (OXPHOS), and EMT expression markers. All cell lines showed additive to synergic interactions for the induction of cytotoxicity caused by the tested combination, as well as an improved pro-apoptotic effect. This effect was accompanied by downregulation of glycolytic, EMT markers, a significant decrease in glucose uptake, extracellular lactate, and a tendency towards increased OXPHOS subunits expression. Interestingly, we observed a better response to the combined therapy in lung cancer cell lines A549 and H1975, which normally have low affinity for TKI treatment. Findings from this study suggest a sensitization to afatinib therapy by metformin in TKI-resistant lung cancer cells, as well as a reduction in cellular glycolytic phenotype.
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