ArticleThe Journal of biological chemistry2015
Gefitinib-mediated reactive oxygen specie (ROS) instigates mitochondrial dysfunction and drug resistance in lung cancer cells.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 99 citations in OpenAlex.
- Persistent TOP1 cleavage complexes in drug-tolerant cells drive adaptive resistance to EGFR-targeted therapies in lung cancer.Science advances · 2026Article
- EGFR inhibitor-resistant lung cancers exhibit collateral sensitivity to a covalent, cysteine-independent KEAP1 oligomerizing molecular bridge.Nature communications · 2026Article
- The inhibitory effect of Osthole on A549 lung adenocarcinoma cells and its biomarker.Scientific reports · 2025Article
- Mitochondria-associated non-coding RNAs and their impact on drug resistance.Frontiers in pharmacology · 2025Review
- Lactylation-Driven IGF2BP3-Mediated Serine Metabolism Reprogramming and RNA m6A-Modification Promotes Lenvatinib Resistance in HCC.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Metabolic profiling and combined therapeutic strategies unveil the cytotoxic potential of selenium-chrysin (SeChry) in NSCLC cells.Bioscience reports · 2024Article
- Promoting reactive oxygen species accumulation to overcome tyrosine kinase inhibitor resistance in cancer.Cancer cell international · 2024Review
- Systematic omics analysis identifies CCR6 as a therapeutic target to overcome cancer resistance to EGFR inhibitors.iScience · 2024Article
- Mitochondrion: Main organelle in orchestrating cancer escape from chemotherapy.Cancer reports (Hoboken, N.J.) · 2024Review
- Article
- The role of m6A methylation in targeted therapy resistance in lung cancer.American journal of cancer research · 2024Review
- Piperlongumine in combination with EGFR tyrosine kinase inhibitors for the treatment of lung cancer cells.Oncology research · 2024Article
- The tyrosine kinase inhibitor Gefitinib reducesmicroPublication biology · 2024Article
- EGFR TKI resistance in lung cancer cells using RNA sequencing and analytical bioinformatics tools.Journal of biomolecular structure & dynamics · 2023Article
- [Cigarette Smoke Induces Gefitinib Resistance in NSCLC Cells via ROS/Sirt3/SOD2 Pathway].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2023Article
- Inhibition of the mitochondria-shaping protein Opa1 restores sensitivity to Gefitinib in a lung adenocarcinomaresistant cell line.Cell death & disease · 2023Article
- RNA methylation and cellular response to oxidative stress-promoting anticancer agents.Cell cycle (Georgetown, Tex.) · 2023Review
- Review
- Review
- Iron imbalance in cancer: Intersection of deficiency and overload.Cancer medicine · 2022Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Therapeutic benefits offered by tyrosine kinase inhibitors (TKIs), such as gefitinib (Iressa) and erlotinib (Tarceva), are limited due to the development of resistance, which contributes to treatment failure and cancer-related mortality. The aim of this study was to elucidate mechanistic insight into cellular perturbations that accompany acquired gefitinib resistance in lung cancer cells. Several lung adenocarcinoma (LAD) cell lines were screened to characterize epidermal growth factor receptor (EGFR) expression and mutation profile. To circumvent intrinsic variations between cell lines with respect to response to drug treatments, we generated gefitinib-resistant H1650 clone by long-term, chronic culture under gefitinib selection of parental cell line. Isogenic cells were analyzed by microarray, Western blot, flow cytometry, and confocal and transmission electron microscope. We observed that although chronic gefitinib treatment provided effective action against its primary target (aberrant EGFR activity), secondary effects resulted in increased cellular reactive oxygen species (ROS). Gefitinib-mediated ROS correlated with epithelial-mesenchymal transition, as well as striking perturbation of mitochondrial morphology and function. However, gefitinib treatment in the presence of ROS scavenger provided a partial rescue of mitochondrial aberrations. Furthermore, withdrawal of gefitinib from previously resistant clones correlated with normalized expression of epithelial-mesenchymal transition genes. These findings demonstrate that chronic gefitinib treatment promotes ROS and mitochondrial dysfunction in lung cancer cells. Antioxidants may alleviate ROS-mediated resistance.
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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.