ArticleBioMed research international2019
Glutathione Peroxidase 1 Promotes NSCLC Resistance to Cisplatin via ROS-Induced Activation of PI3K/AKT Pathway.
Article in BioMed research international, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 83 citations in OpenAlex.
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- Exercise Training Stimulates the Release of Glutathione Peroxidase 1 (GPX1)-Enriched Extracellular Vesicles That Promote Angiogenesis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Nanomedicine-powered redox homeostasis modulation: Disrupting antioxidant systems and inducing oxidative stress for precision tumor therapy.Materials today. Bio · 2026Review
- Hibernating bear serum triggers an anti-fibrotic signature in human fibroblasts, involving ECM remodeling and MAPK signaling activation.Scientific reports · 2026Article
- Glutathione Peroxidases 1 and 3 Immunoscores in Clear Cell Renal Cell Carcinoma: New Insights from a Case-Series Study.Oncology research · 2026Article
- Vismodegib Potentiates Marine Antimicrobial Peptide Tilapia Piscidin 4-Induced Cytotoxicity in Human Non-Small Cell Lung Cancer Cells.Probiotics and antimicrobial proteins · 2025Article
- Anticancer Effect of Nature-Inspired Indolizine-Based Pentathiepines in 2D and 3D Cellular Model.Cancers · 2025Article
- GPX1 confers resistance to metabolic stress in BCR/ABL-T315I mutant chronic myeloid leukemia cells.Cell death discovery · 2025Article
- Selenium and Selenoproteins: Mechanisms, Health Functions, and Emerging Applications.Molecules (Basel, Switzerland) · 2025Review
- Advances in Selenium and Related Compounds Inhibiting Multi-Organ Fibrosis.Drug design, development and therapy · 2025Review
- GPX1 expression promotes stemness and aggressiveness in myxoid liposarcomas.International journal of biological sciences · 2025Article
- Glutathione-Dependent Pathways in Cancer Cells.International journal of molecular sciences · 2024Review
- Mitochondrion: Main organelle in orchestrating cancer escape from chemotherapy.Cancer reports (Hoboken, N.J.) · 2024Review
- Nrf2-Mediated Antioxidant Response and Drug Efflux Transporters Upregulation as Possible Mechanisms of Resistance in Photodynamic Therapy of Cancers.OncoTargets and therapy · 2024Review
- Serum trace element levels and activity of enzymes associated with oxidative stress in endometriosis and endometrial cancer.FEBS open bio · 2024Article
- Elevation of LEM Domain Containing 1 Predicts Poor Prognosis of NSCLC Patients and Triggers Malignant Stemness and Invasion of NSCLC Cells by Stimulating PI3K/AKT Pathway.Current molecular medicine · 2024Article
- Kinetic Effects of Transferrin-Conjugated Gold Nanoparticles on the Antioxidant Glutathione-Thioredoxin Pathway.Antioxidants (Basel, Switzerland) · 2023Article
- Spatially Resolved Proteomic and Transcriptomic Profiling of Anaplastic Lymphoma Kinase-Rearranged Pulmonary Adenocarcinomas Reveals Key Players in Inter- and Intratumoral Heterogeneity.International journal of molecular sciences · 2023Article
- The Role of Selenium and Manganese in the Formation, Diagnosis and Treatment of Cervical, Endometrial and Ovarian Cancer.International journal of molecular sciences · 2023Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeReactive oxygen species (ROS)-induced cytotoxicity is an important mechanism by which cisplatin kills tumor cells. Glutathione peroxidase family (GPXs) is an important member of antioxidant system which metabolizes intracellular ROS and maintains homeostasis of cells. Altered expressions of GPXs enzymes, especially GPX1, have been described in a variety of human cancers. However, their functional roles in cisplatin-based chemoresistance in human malignancies including non-small cell lung cancer have never been explored.
methodsA panel of NSCLC cell lines were selected for this study. GPX1 expression was detected using quantitative RT-PCR and Western blot. Cisplatin-induced cell killing was analyzed by CCK8 assay. Intracellular ROS levels were detected by fluorescence-based flow cytometry analysis. In vitro overexpression and knockdown of GPX1 expression were performed using GPX1 expression vector and siRNA approaches. Protein levels of PTEN, NF-
resultsGPX1 expression was upregulated in a subset of NSCLC cell lines resistant to cisplatin treatment. Expression vector-mediated forced overexpression of GPX1 significantly increased cisplatin resistance in NSCLC cell lines, whereas RNA inference-mediated downregulation of GPX1 could restore sensitivity to cisplatin. Overexpression of GPX1 significantly suppressed elevation of intracellular ROS and activation of AKT pathway when NSCLC cell lines were exposed to different concentrations of cisplatin. Activation of the AKT pathway inhibited proapoptotic cascade and subsequently led to cisplatin resistance in NSCLC cells. Inhibition of NF-
conclusionsOur findings suggested that overexpression of GPX1 is a novel molecular mechanism for cisplatin-based chemoresistance in NSCLC. GPX1 overexpression blocks cisplatin-induced ROS intracellular accumulation, activates PI3K-AKT pathway by increased AKT phosphorylation, and further leads to cisplatin resistance in NSCLC cells. Inhibition of NF-
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