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Statins inhibit 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase and may affect tumor cell fitness via the mevalonate pathway, mitochondrial function, and redox homeostasis. We systematically compared seven statins in patient-derived PDAC cell lines and related viability effects to mitochondrial, redox, cell-cycle, apoptotic, and metabolic responses. Statins were tested in three PDAC cell lines (PDAC-1\/2\/3) using MTT assays (5\u201320 \u00b5M; 24\u2013120 h). Based on MTT responses, mechanistic profiling was performed after 72 h at 20 \u00b5M concentration using lipophilic statins, including apoptosis (Annexin V\/7-AAD), cell-cycle distribution, mitochondrial membrane potential (\u0394\u03c8m), intracellular ROS, and 1H-NMR quantification of intracellular and extracellular metabolites. Statins reduced viability in a concentration- and time-dependent manner, with lipophilic statins more active than hydrophilic. PDAC-1 was highly sensitive, PDAC-3 intermediate, and PDAC-2 comparatively resistant. PDAC-1 and PDAC-3 showed G0\/G1 accumulation, \u0394\u03c8m depolarization, reactive oxygen species (ROS) elevation, and Annexin V\u2013positive apoptosis, whereas PDAC-2 (high basal ROS) showed ROS reduction and limited apoptosis despite \u0394\u03c8m loss. Metabolomics indicated reduced glucose and amino-acid utilization and lactate secretion while preserving line-specific metabolic fingerprints. PDAC cell lines display marked inter-tumoral heterogeneity in statin responses, supporting evaluation of statins as chemosensitizing adjuvants in functionally guided PDAC treatment strategies.<\/jats:p>","DOI":"10.3390\/ijms27072972","type":"journal-article","created":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T09:11:14Z","timestamp":1774429874000},"page":"2972","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Anti-Tumor Effects of Statins in Pancreatic Ductal Adenocarcinoma Cells"],"prefix":"10.3390","volume":"27","author":[{"given":"Veronika","family":"Kuch\u00e1rikov\u00e1","sequence":"first","affiliation":[{"name":"Biomedical Centre Martin, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Mal\u00e1 Hora 4C, 036 01 Martin, Slovakia"},{"name":"Department of Medical Biochemistry, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Mal\u00e1 Hora 4D, 036 01 Martin, Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zuzana","family":"Hatokov\u00e1","sequence":"additional","affiliation":[{"name":"Biomedical Centre Martin, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Mal\u00e1 Hora 4C, 036 01 Martin, Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6840-383X","authenticated-orcid":false,"given":"Eva","family":"Baranovi\u010dov\u00e1","sequence":"additional","affiliation":[{"name":"Biomedical Centre Martin, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Mal\u00e1 Hora 4C, 036 01 Martin, Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-6417-1742","authenticated-orcid":false,"given":"Bibi\u00e1na","family":"Ba\u010furov\u00e1","sequence":"additional","affiliation":[{"name":"Biomedical Centre Martin, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Mal\u00e1 Hora 4C, 036 01 Martin, Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tereza","family":"Pavli\u0161ov\u00e1","sequence":"additional","affiliation":[{"name":"Biomedical Centre Martin, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Mal\u00e1 Hora 4C, 036 01 Martin, Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-5677-4010","authenticated-orcid":false,"given":"Lucia","family":"Kot\u00fa\u013eov\u00e1","sequence":"additional","affiliation":[{"name":"Biomedical Centre Martin, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Mal\u00e1 Hora 4C, 036 01 Martin, Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michal","family":"Kalman","sequence":"additional","affiliation":[{"name":"Department of Pathological Anatomy, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava and University Hospital Martin, Koll\u00e1rov\u00e1 2, 036 01 Martin, Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juraj","family":"Marcinek","sequence":"additional","affiliation":[{"name":"Department of Pathological Anatomy, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava and University Hospital Martin, Koll\u00e1rov\u00e1 2, 036 01 Martin, Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"O\u013ega","family":"Chodelkov\u00e1","sequence":"additional","affiliation":[{"name":"Biomedical Centre Martin, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Mal\u00e1 Hora 4C, 036 01 Martin, Slovakia"},{"name":"Department of Medical Biochemistry, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Mal\u00e1 Hora 4D, 036 01 Martin, Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Slavom\u00edra","family":"Nov\u00e1kov\u00e1","sequence":"additional","affiliation":[{"name":"Biomedical Centre Martin, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Mal\u00e1 Hora 4C, 036 01 Martin, Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00e1n","family":"Strn\u00e1del","sequence":"additional","affiliation":[{"name":"Biomedical Centre Martin, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Mal\u00e1 Hora 4C, 036 01 Martin, Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6854-2338","authenticated-orcid":false,"given":"Henrieta","family":"\u0160kovierov\u00e1","sequence":"additional","affiliation":[{"name":"Biomedical Centre Martin, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Mal\u00e1 Hora 4C, 036 01 Martin, 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Rep."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"4500","DOI":"10.12998\/wjcc.v9.i18.4500","article-title":"Anti-Tumor Effect of Statin on Pancreatic Adenocarcinoma: From Concept to Precision Medicine","volume":"9","author":"Huang","year":"2021","journal-title":"World J. Clin. Cases"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"165968","DOI":"10.1016\/j.bbadis.2020.165968","article-title":"Pleiotropic Effects of Statins: A Focus on Cancer","volume":"1866","author":"Ahmadi","year":"2020","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1186\/s13046-021-02041-2","article-title":"Statins: A Repurposed Drug to Fight Cancer","volume":"40","author":"Jiang","year":"2021","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"188351","DOI":"10.1016\/j.bbcan.2020.188351","article-title":"Cholesterol and beyond-The Role of the Mevalonate Pathway in Cancer Biology","volume":"1873","author":"Rauner","year":"2020","journal-title":"Biochim. Biophys. Acta Rev. Cancer"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Khatiwada, N., and Hong, Z. (2024). Potential Benefits and Risks Associated with the Use of Statins. Pharmaceutics, 16.","DOI":"10.3390\/pharmaceutics16020214"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Liu, C., Chen, H., Hu, B., Shi, J., Chen, Y., and Huang, K. (2023). New Insights into the Therapeutic Potentials of Statins in Cancer. Front. Pharmacol., 14.","DOI":"10.3389\/fphar.2023.1188926"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1007\/s00253-002-0932-9","article-title":"Biosynthesis and Biotechnological Production of Statins by Filamentous Fungi and Application of These Cholesterol-Lowering Drugs","volume":"58","author":"Manzoni","year":"2002","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2054","DOI":"10.1128\/AEM.02820-06","article-title":"Efficient Synthesis of Simvastatin by Use of Whole-Cell Biocatalysis","volume":"73","author":"Xie","year":"2007","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Murphy, C., Deplazes, E., Cranfield, C.G., and Garcia, A. (2020). The Role of Structure and Biophysical Properties in the Pleiotropic Effects of Statins. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21228745"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.dld.2018.09.007","article-title":"Statin Use Is Associated to a Reduced Risk of Pancreatic Cancer: A Meta-Analysis","volume":"51","author":"Archibugi","year":"2019","journal-title":"Dig. Liver Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1097\/MPA.0000000000001226","article-title":"Statin Use and Risk of Pancreatic Cancer: An Updated Meta-Analysis of 26 Studies","volume":"48","author":"Zhang","year":"2019","journal-title":"Pancreas"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Tilija Pun, N., and Jeong, C.-H. (2021). Statin as a Potential Chemotherapeutic Agent: Current Updates as a Monotherapy, Combination Therapy, and Treatment for Anti-Cancer Drug Resistance. Pharmaceuticals, 14.","DOI":"10.3390\/ph14050470"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.semcancer.2020.08.002","article-title":"Effects of Statins on Brain Tumors: A Review","volume":"73","author":"Afshari","year":"2021","journal-title":"Semin. Cancer Biol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Gyoten, M., Luo, Y., Fujiwara-Tani, R., Mori, S., Ogata, R., Kishi, S., and Kuniyasu, H. (2023). Lovastatin Treatment Inducing Apoptosis in Human Pancreatic Cancer Cells by Inhibiting Cholesterol Rafts in Plasma Membrane and Mitochondria. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms242316814"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"111858","DOI":"10.1016\/j.biopha.2021.111858","article-title":"The Potential Use of Simvastatin for Cancer Treatment: A Review","volume":"141","author":"Duarte","year":"2021","journal-title":"Biomed. Pharmacother."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1038\/s41374-021-00690-7","article-title":"Fluvastatin Sensitizes Pancreatic Cancer Cells toward Radiation Therapy and Suppresses Radiation- and\/or TGF-\u03b2-Induced Tumor-Associated Fibrosis","volume":"102","author":"Mohapatra","year":"2022","journal-title":"Lab. Investig."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Chen, C.-Y., Yang, Y.-F., Wang, P.C., Shan, L., Lin, S., Chen, P.-J., Chen, Y.-J., Chiang, H.-S., Lin, J.-T., and Hung, C.-F. (2022). Simvastatin Attenuated Tumor Growth in Different Pancreatic Tumor Animal Models. Pharmaceuticals, 15.","DOI":"10.3390\/ph15111408"},{"key":"ref_19","first-page":"2041","article-title":"Statins Exert Anti-Growth Effects by Suppressing YAP\/TAZ Expressions via JNK Signal Activation and Eliminate the Immune Suppression by Downregulating PD-L1 Expression in Pancreatic Cancer","volume":"13","author":"Uemura","year":"2023","journal-title":"Am. J. Cancer Res."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Sadowska, A., Osi\u0144ski, P., Roztocka, A., Kaczmarz-Chojnacka, K., Zapora, E., Sawicka, D., and Car, H. (2023). Statins\u2014From Fungi to Pharmacy. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25010466"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"11830","DOI":"10.1038\/s41598-024-62615-w","article-title":"Highly Variable Biological Effects of Statins on Cancer, Non-Cancer, and Stem Cells in Vitro","volume":"14","author":"Ruml","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_22","first-page":"e2078","article-title":"Statins as Anti-Tumor Agents: A Paradigm for Repurposed Drugs","volume":"7","author":"Tripathi","year":"2024","journal-title":"Cancer Rep."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"8186","DOI":"10.1096\/fj.201802723R","article-title":"Statin-Dependent Modulation of Mitochondrial Metabolism in Cancer Cells Is Independent of Cholesterol Content","volume":"33","author":"Christie","year":"2019","journal-title":"FASEB J."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Huang, X., Liang, N., Zhang, F., Lin, W., and Ma, W. (2024). Lovastatin-Induced Mitochondrial Oxidative Stress Leads to the Release of mtDNA to Promote Apoptosis by Activating cGAS-STING Pathway in Human Colorectal Cancer Cells. Antioxidants, 13.","DOI":"10.3390\/antiox13060679"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.gene.2015.08.009","article-title":"Pitfalls of the MTT Assay: Direct and off-Target Effects of Inhibitors Can Result in over\/Underestimation of Cell Viability","volume":"574","author":"Stepanenko","year":"2015","journal-title":"Gene"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Ghasemi, M., Turnbull, T., Sebastian, S., and Kempson, I. (2021). The MTT Assay: Utility, Limitations, Pitfalls, and Interpretation in Bulk and Single-Cell Analysis. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222312827"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3945","DOI":"10.1111\/cas.15068","article-title":"Reactive Oxygen Species in Cancer: Current Findings and Future Directions","volume":"112","author":"Nakamura","year":"2021","journal-title":"Cancer Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1080\/07357900701874658","article-title":"Statin-Induced Inhibition of MCF-7 Breast Cancer Cell Proliferation Is Related to Cell Cycle Arrest and Apoptotic and Necrotic Cell Death Mediated by an Enhanced Oxidative Stress","volume":"26","author":"Varela","year":"2008","journal-title":"Cancer Investig."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.toxlet.2010.09.010","article-title":"Involvement of Oxidative Stress in Simvastatin-Induced Apoptosis of Murine CT26 Colon Carcinoma Cells","volume":"199","author":"Qi","year":"2010","journal-title":"Toxicol. Lett."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"262","DOI":"10.3892\/ijo.2013.1933","article-title":"Synergistic Induction of Apoptosis by Sulindac and Simvastatin in A549 Human Lung Cancer Cells via Reactive Oxygen Species-Dependent Mitochondrial Dysfunction","volume":"43","author":"Hwang","year":"2013","journal-title":"Int. J. Oncol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1161\/01.CIR.0000138743.09012.93","article-title":"Antioxidant Effects of Statins via S-Nitrosylation and Activation of Thioredoxin in Endothelial Cells: A Novel Vasculoprotective Function of Statins","volume":"110","author":"Haendeler","year":"2004","journal-title":"Circulation"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1089\/ars.2013.5430","article-title":"Statins as Regulators of Redox State in the Vascular Endothelium: Beyond Lipid Lowering","volume":"20","author":"Margaritis","year":"2014","journal-title":"Antioxid. Redox Signal."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Mansouri, A., Reiner, \u017d., Ruscica, M., Tedeschi-Reiner, E., Radbakhsh, S., Bagheri Ekta, M., and Sahebkar, A. (2022). Antioxidant Effects of Statins by Modulating Nrf2 and Nrf2\/HO-1 Signaling in Different Diseases. J. Clin. Med., 11.","DOI":"10.3390\/jcm11051313"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1002\/jcsm.12654","article-title":"Effects of Statins on Mitochondrial Pathways","volume":"12","author":"Mollazadeh","year":"2021","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"692","DOI":"10.21037\/tlcr.2019.09.08","article-title":"Current Perspectives on Statins as Potential Anti-Cancer Therapeutics: Clinical Outcomes and Underlying Molecular Mechanisms","volume":"8","year":"2019","journal-title":"Transl. Lung Cancer Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"11863","DOI":"10.1038\/s41598-017-11070-x","article-title":"Atorvastatin but Not Pravastatin Impairs Mitochondrial Function in Human Pancreatic Islets and Rat \u03b2-Cells. Direct Effect of Oxidative Stress","volume":"7","author":"Urbano","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"110056","DOI":"10.1016\/j.celrep.2021.110056","article-title":"Statins Affect Cancer Cell Plasticity with Distinct Consequences for Tumor Progression and Metastasis","volume":"37","author":"Dorsch","year":"2021","journal-title":"Cell Rep."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Mengual, D., Medrano, L.E., Villamizar-Villamizar, W., Osorio-Llanes, E., Mendoza-Torres, E., and Bol\u00edvar, S. (2022). Novel Effects of Statins on Cancer via Autophagy. Pharmaceuticals, 15.","DOI":"10.3390\/ph15060648"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1158\/jcr.1925.148","article-title":"The Metabolism of Carcinoma Cells1","volume":"9","author":"Warburg","year":"1925","journal-title":"J. Cancer Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3678","DOI":"10.1172\/JCI69600","article-title":"Glutamine and Cancer: Cell Biology, Physiology, and Clinical Opportunities","volume":"123","author":"Hensley","year":"2013","journal-title":"J. Clin. Investig."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"82","DOI":"10.3892\/ol.2020.12343","article-title":"Atorvastatin Potentiates the Chemosensitivity of Human Liver Cancer Cells to Cisplatin via Downregulating YAP1","volume":"21","author":"Guo","year":"2020","journal-title":"Oncol. Lett."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"165","DOI":"10.4149\/neo_2021_210924N1360","article-title":"Establishment of PANDA\u2014A New Human Pancreatic Ductal Adenocarcinoma Cell Line with 3D Cell Culture Technology","volume":"69","author":"Zahumenska","year":"2022","journal-title":"Neoplasma"},{"key":"ref_43","first-page":"149","article-title":"Effect of Long-Term Culture on the Biological and Morphological Characteristics of Human Adipose Tissue-Derived Stem Cells","volume":"68","author":"Danisovic","year":"2017","journal-title":"J. Physiol. Pharmacol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1007\/s00216-010-4425-x","article-title":"Metabolite Extraction from Adherently Growing Mammalian Cells for Metabolomics Studies: Optimization of Harvesting and Extraction Protocols","volume":"399","author":"Dettmer","year":"2011","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Andresen, C., Boch, T., Gegner, H.M., Mechtel, N., Narr, A., Birgin, E., Rasbach, E., Rahbari, N., Trumpp, A., and Poschet, G. (2022). Comparison of Extraction Methods for Intracellular Metabolomics of Human Tissues. Front. Mol. Biosci., 9.","DOI":"10.3389\/fmolb.2022.932261"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Nov\u00e1kov\u00e1, S., Baranovi\u010dov\u00e1, E., Hatokov\u00e1, Z., Beke, G., P\u00e1le\u0161ov\u00e1, J., Z\u00e1humensk\u00e1, R., Ba\u010furov\u00e1, B., Jan\u00ed\u010dkov\u00e1, M., Strn\u00e1del, J., and Hala\u0161ov\u00e1, E. (2024). Comparison of Various Extraction Approaches for Optimized Preparation of Intracellular Metabolites from Human Mesenchymal Stem Cells and Fibroblasts for NMR-Based Study. Metabolites, 14.","DOI":"10.3390\/metabo14050268"},{"key":"ref_47","unstructured":"R Core Team (2024). R: A Language and Environment for Statistical Computing, R Foundation for Statistical Computing. Available online: https:\/\/www.r-project.org\/."},{"key":"ref_48","unstructured":"Fox, J., Weisberg, S., and Price, B. (2026, March 19). car: Companion to Applied Regression, Version 3.1-3. Available online: https:\/\/cran.r-project.org\/web\/packages\/car\/car.pdf."},{"key":"ref_49","unstructured":"Lenth, R.V. (2026, March 19). emmeans: Estimated Marginal Means, aka Least-Squares Means, Version 1.11.1. Available online: https:\/\/cran.r-project.org\/web\/packages\/emmeans\/emmeans.pdf."},{"key":"ref_50","unstructured":"Kassambara, A. (2026, March 19). ggpubr: \u2018ggplot2\u2019 Based Publication Ready Plots, Version 0.6.0. Available online: https:\/\/cran.r-project.org\/web\/packages\/ggpubr\/ggpubr.pdf."},{"key":"ref_51","unstructured":"Bates, D., Maechler, M., Bolker, B., and Walker, S. (2026, March 19). lme4: Linear Mixed-Effects Models Using \u2018Eigen\u2019 and S4, Version 1.1-37. Available online: https:\/\/cran.r-project.org\/web\/packages\/lme4\/lme4.pdf."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"5791","DOI":"10.1158\/1078-0432.CCR-20-1967","article-title":"Statins as Anticancer Agents in the Era of Precision Medicine","volume":"26","author":"Longo","year":"2020","journal-title":"Clin. Cancer Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1856","DOI":"10.1016\/j.biopha.2018.09.122","article-title":"Effects of Statins on the Chemoresistance-The Antagonistic Drug-Drug Interactions versus the Anti-Cancer Effects","volume":"108","author":"Ahmadi","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"849","DOI":"10.5966\/sctm.2013-0204","article-title":"Simvastatin Radiosensitizes Differentiated and Stem-Like Breast Cancer Cell Lines and Is Associated with Improved Local Control in Inflammatory Breast Cancer Patients Treated with Postmastectomy Radiation","volume":"3","author":"Lacerda","year":"2014","journal-title":"Stem Cells Transl. Med"},{"key":"ref_55","unstructured":"Wickham, H., Fran\u00e7ois, R., Henry, L., M\u00fcller, K., and Vaughan, D. (2026, March 19). dplyr: A Grammar of Data Manipulation, Version 1.1.4. Available online: https:\/\/cran.r-project.org\/web\/packages\/dplyr\/dplyr.pdf."},{"key":"ref_56","unstructured":"Gohel, D., and Skintzos, P. (2026, March 19). flextable: Functions for Tabular Reporting, Version 0.9.8. Available online: https:\/\/cran.r-project.org\/web\/packages\/flextable\/flextable.pdf."},{"key":"ref_57","unstructured":"Wickham, H., Chang, W., Henry, L., Pedersen, T.L., Takahashi, K., Wilke, C., Woo, K., Yutani, H., Dunnington, D., and van den Brand, T. (2026, March 19). ggplot2: Create Elegant Data Visualisations Using the Grammar of Graphics, Version 3.5.2. Available online: https:\/\/cran.r-project.org\/web\/packages\/ggplot2\/ggplot2.pdf."},{"key":"ref_58","unstructured":"Simpson, G.L. (2026, March 19). gratia: Graceful \u2018ggplot\u2019-Based Graphics and Other Functions for GAMs Fitted Using \u2018mgcv\u2019, Version 0.10.0. Available online: https:\/\/cran.r-project.org\/web\/packages\/gratia\/gratia.pdf."},{"key":"ref_59","unstructured":"Sjoberg, D.D., Larmarange, J., Curry, M., de la Rua, E., Lavery, J., Whiting, K., Zabor, E.C., Bai, X., Barret, M., and Dril, E. (2026, March 19). gtsummary: Presentation-Ready Data Summary and Analytic Result Tables, Version 2.5.0. Available online: https:\/\/cran.r-project.org\/web\/packages\/gtsummary\/gtsummary.pdf."},{"key":"ref_60","unstructured":"L\u00fcdecke, D. (2026, March 19). sjPlot: Data Visualization for Statistics in Social Science, Version 2.8.17. Available online: https:\/\/cran.r-project.org\/web\/packages\/sjPlot\/sjPlot.pdf."},{"key":"ref_61","unstructured":"Wickham, H., Vaughan, D., and Girlich, M. (2026, March 19). tidyr: Tidy Messy Data, Version 1.3.1. Available online: https:\/\/cran.r-project.org\/web\/packages\/tidyr\/tidyr.pdf."},{"key":"ref_62","unstructured":"Sarkar, D. (2026, March 19). lattice: Trellis Graphics for R, Version 0.22-7. Available online: https:\/\/cran.r-project.org\/web\/packages\/lattice\/lattice.pdf."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/7\/2972\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T05:20:58Z","timestamp":1774588858000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/7\/2972"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,25]]},"references-count":62,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["ijms27072972"],"URL":"https:\/\/doi.org\/10.3390\/ijms27072972","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,25]]}}}