ArticleScientific reports2020
Delineation of cell death mechanisms induced by synergistic effects of statins and erlotinib in non-small cell lung cancer cell (NSCLC) lines.
Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 51 citations in OpenAlex.
- Article
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- Exploring Synergistic Potential of Sorafenib and Atorvastatin to Launch Apoptosis and Ferroptosis-driven Mixed Cell Death Mechanism in Colorectal Cancer.AAPS PharmSciTech · 2026Article
- METTL7A inhibits progression of colorectal cancer through the SREBP1 / FDFT1 / SQLE / CYP51A1 / cholesterol metabolic pathway.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- Therapy-induced cholesterol biosynthesis drives lung cancer dormancy and drug resistance.The Journal of clinical investigation · 2026Article
- Preliminary Exploration of Fluvastatin Inhibiting Proliferation, Migration and Invasion of Lung Cancer Cells and Reversing Paclitaxel Resistance: Mechanism Exploration Based on Multi-Omics Analysis.Drug design, development and therapy · 2026Article
- The role of statins in the treatment of lung cancer with epidermal growth factor receptor-tyrosine kinase inhibitors: a protocol for systematic review and meta-analysis.Frontiers in medicine · 2026Article
- Targeting regulated cell death pathways in lung cancer: mechanisms, therapeutic strategies, and clinical translation.Frontiers in immunology · 2026Review
- Statins attenuate PD-L1 sorting to small extracellular vesicles dependent on ubiquitin-like 3 modification.Scientific reports · 2025Article
- Intracellular cholesterol: new functions and therapeutic approaches in NSCLC EGFR-TKI resistance.Lipids in health and disease · 2025Review
- Statins as potential adjuvant therapy in lung cancer: a narrative review.Journal of thoracic disease · 2025Review
- Thermal cycling‑hyperthermia sensitizes non‑small cell lung cancer A549 cells to EGFR tyrosine kinase inhibitor erlotinib.Oncology reports · 2025Article
- Chitosan capped-NLCs enhanced codelivery of gefitinib and simvastatin into MDR HCC: impact of compositions on cell death, JNK3, and Telomerase.Oncology research · 2025Article
- Gemcitabine-loaded chitosan nanoparticles enhanced apoptotic and ferroptotic response of gemcitabine treatment alone in the pancreatic cancer cells in vitro.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- Molecular Mechanisms Underlying the Anticancer Properties of Pitavastatin against Cervical Cancer Cells.International journal of molecular sciences · 2024Article
- Erlotinib Treatment in Colorectal Cancer Suppresses Autophagy Based onCurrent issues in molecular biology · 2024Article
- Induction of resistance to neurotrophic tropomyosin-receptor kinase inhibitors by HMGCS2 via a mevalonate pathway.Cancer medicine · 2024Article
- Energy metabolism as the hub of advanced non-small cell lung cancer management: a comprehensive view in the framework of predictive, preventive, and personalized medicine.The EPMA journal · 2024Review
- Simvastatin Overcomes Resistance to Tyrosine Kinase Inhibitors in Patient-derived, Oncogene-driven Lung Adenocarcinoma Models.Molecular cancer therapeutics · 2024Article
- EGFR-driven lung adenocarcinomas coopt alveolar macrophage metabolism and function to support EGFR signaling and growth.Cancer discovery · 2024Article
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) have been shown to overcome tyrosine kinase inhibitor (TKI) resistance in epithelial growth factor receptor (EGFR) mutated non-small cell lung cancer (NSCLC) cells in vivo and in vitro. However, little is known about the putative induction of non-apoptotic cell death pathways by statins. We investigated the effects of pitavastatin and fluvastatin alone or in combination with erlotinib in three NSCLC cell lines and examined the activation of different cell death pathways. We assessed apoptosis via fluorometric caspase assay and poly (ADP-ribose) polymerase 1 (PARP) cleavage. Furthermore, annexinV/propidium iodide (PI) flow cytometry was performed. Small molecule inhibitors benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone (zVAD), necrostatin 1 (Nec1), ferrostatin 1 (Fer1), Ac-Lys-Lys-Norleucinal (Calp1) were used to characterise cell death pathway(s) putatively (co-)activated by pitavastatin/erlotinib co-treatment. Synergism was calculated by additivity and isobolographic analyses. Pitavastatin and fluvastatin induced cell death in EGFR TKI resistant NSCLC cells lines A549, Calu6 and H1993 as shown by caspase 3 activation and PARP cleavage. Co-treatment of cells with pitavastatin and the EGFR TKI erlotinib resulted in synergistically enhanced cytotoxicity compared to pitavastatin monotherapy. Flow cytometry indicated the induction of alternative regulated cell death pathways. However, only co-treatment with mevalonic acid (Mev) or the pan-caspase inhibitor zVAD could restore cell viability. The results show that cytotoxicity mediated by statin/erlotinib co-treatment is synergistic and can overcome erlotinib resistance in K-ras mutated NSCLC and relies only on apoptosis.
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