{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T06:10:21Z","timestamp":1791526221574,"version":"4.3.4"},"reference-count":66,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T00:00:00Z","timestamp":1765843200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Aberrant paracrine cytokine signaling and dysregulated signal transduction are critical drivers of tumor progression and therapeutic resistance in aggressive cancers such as non-small cell lung cancer and triple-negative breast cancer. This study aimed to explore a dual-targeting strategy using mebendazole, a repurposed anti-parasitic agent known to disrupt microtubules, in combination with gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor. The objective was to assess the combinatorial impact on cell viability and key regulatory pathways involved in inflammation, mitotic control, and nuclear transport.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Human lung adenocarcinoma (A549) and triple-negative breast cancer (MDA-MB-231) cell lines were treated with mebendazole, gefitinib, or a combination of both. Cell viability in both the cell lines was investigated using the MTT assay, while transcriptional profiling was conducted exclusively in the A549 NSCLC cell line to assess cytokine and regulatory gene modulation. Quantitative reverse transcription polymerase chain reaction was performed to evaluate changes in the expression of inflammatory cytokines (interleukin-1 beta, interleukin-6, TNF-alpha, IFN-gamma) and regulatory genes (MMP-2, STAT 4, RAN, and RCC1).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Combined treatment with gefitinib (1 \u00b5M) and mebendazole (0.5 \u00b5M) elicited a pronounced synergistic cytotoxic response, reducing cell viability to ~8\u201310% in A549 and ~15% in MDA-MB-231 cells\u2014representing an additional &gt;50% and ~30\u201340% decrease, respectively, compared to the most effective single-agent treatment- gefitinib 1 \u00b5M. Gene expression analysis revealed significant downregulation of pro-inflammatory cytokines and alterations in genes involved in mitotic regulation and nuclear transport. These changes suggest impaired intracellular signaling and reduced tumor-supportive microenvironmental interactions. The dual approach disrupted both cytoskeletal architecture and receptor-mediated signal transduction, pointing to a multifaceted mechanism of action.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The combination of mebendazole and gefitinib effectively suppresses tumor cell viability and modulates key pathways involved in cancer progression. By targeting cytoskeletal integrity and EGFR signaling, it may disrupt cytokine and tumor\u2013microenvironment interactions, supporting further exploration as a strategy to overcome resistance in lung and breast cancers.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0338027","type":"journal-article","created":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T18:22:29Z","timestamp":1765909349000},"page":"e0338027","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["Disruption of epidermal growth factor receptor signaling and cytoskeletal dynamics by mebendazole and gefitinib synergistically impairs paracrine cytokine signaling in non-small cell lung cancer and triple-negative breast cancer Cell 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Arman","family":"Rabbani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yahia","family":"El-Tanani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Sutherland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frezah","family":"Muhana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,12,16]]},"reference":[{"issue":"12","key":"pone.0338027.ref001","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1007\/s12094-015-1455-z","article-title":"SEOM clinical guidelines for the treatment of non-small cell lung cancer (NSCLC) 2015","volume":"17","author":"R Garc\u00eda-Campelo","year":"2015","journal-title":"Clin Transl 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Liu","year":"2021","journal-title":"Theranostics"},{"issue":"2","key":"pone.0338027.ref036","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1158\/1078-0432.CCR-11-2035","article-title":"Ran is a potential therapeutic target for cancer cells with molecular changes associated with activation of the PI3K\/Akt\/mTORC1 and Ras\/MEK\/ERK pathways","volume":"18","author":"H-F Yuen","year":"2012","journal-title":"Clin Cancer Res"},{"issue":"12","key":"pone.0338027.ref037","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.2217\/nnm-2023-0351","article-title":"In vivo evaluation of mebendazole and Ran GTPase inhibition in breast cancer model system","volume":"19","author":"B Abu-Hdaib","year":"2024","journal-title":"Nanomedicine (Lond)"},{"issue":"2","key":"pone.0338027.ref038","doi-asserted-by":"crossref","first-page":"1412","DOI":"10.21037\/jtd-23-1978","article-title":"Mebendazole induces apoptosis and inhibits migration via the reactive oxygen species-mediated STAT3 signaling downregulation in non-small cell lung cancer","volume":"16","author":"Z Liang","year":"2024","journal-title":"J Thorac Dis"},{"issue":"13","key":"pone.0338027.ref039","first-page":"1201","article-title":"The anthelmintic drug mebendazole induces mitotic arrest and apoptosis by depolymerizing tubulin in non-small cell lung cancer cells","volume":"1","author":"J Sasaki","year":"2002","journal-title":"Mol Cancer Ther"},{"issue":"10","key":"pone.0338027.ref040","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1007\/s12272-009-2002-7","article-title":"Gefitinib induces apoptosis and decreases telomerase activity in MDA-MB-231 human breast cancer cells","volume":"32","author":"D-O Moon","year":"2009","journal-title":"Arch Pharm Res"},{"issue":"1","key":"pone.0338027.ref041","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.1080\/10717544.2017.1384862","article-title":"In vitro and in vivo antitumor effect of gefitinib nanoparticles on human lung cancer","volume":"24","author":"XL Ni","year":"2017","journal-title":"Drug Deliv"},{"issue":"6","key":"pone.0338027.ref042","article-title":"Analysis of cell viability by the MTT assay","volume":"2018","author":"P Kumar","year":"2018","journal-title":"Cold Spring Harb Protoc"},{"key":"pone.0338027.ref043","first-page":"137","article-title":"MTT assays","volume":"43","author":"R Supino","year":"1995","journal-title":"Methods Mol Biol"},{"issue":"11","key":"pone.0338027.ref044","doi-asserted-by":"crossref","first-page":"1655","DOI":"10.1080\/17425247.2020.1813714","article-title":"Co-delivery of a RanGTP inhibitory peptide and doxorubicin using dual-loaded liposomal carriers to combat chemotherapeutic resistance in breast cancer cells","volume":"17","author":"Y Haggag","year":"2020","journal-title":"Expert Opin Drug Deliv"},{"issue":"5","key":"pone.0338027.ref045","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1007\/s13346-020-00750-3","article-title":"Nanoencapsulation of sophorolipids in PEGylated poly(lactide-co-glycolide) as a novel approach to target colon carcinoma in the murine model","volume":"10","author":"Y Haggag","year":"2020","journal-title":"Drug Deliv Transl Res"},{"issue":"7","key":"pone.0338027.ref046","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1093\/jnci\/djt028","article-title":"RanGTPase: a candidate for Myc-mediated cancer progression","volume":"105","author":"H-F Yuen","year":"2013","journal-title":"J Natl Cancer Inst"},{"key":"pone.0338027.ref047","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1007\/978-981-99-4657-0_2","article-title":"Cytokines and chemokines in tumor growth and progression","volume-title":"Cytokine and chemokine networks in cancer","author":"MA Mir","year":"2023"},{"key":"pone.0338027.ref048","doi-asserted-by":"crossref","first-page":"121046","DOI":"10.1016\/j.lfs.2022.121046","article-title":"Matrix metalloproteinase 2 is a target of the RAN-GTP pathway and mediates migration, invasion and metastasis in human breast cancer","volume":"310","author":"M El-Tanani","year":"2022","journal-title":"Life Sci"},{"issue":"1","key":"pone.0338027.ref049","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1136\/jclinpath-2020-206871","article-title":"Ran GTPase is an independent prognostic marker in malignant melanoma which promotes tumour cell migration and invasion","volume":"75","author":"S Elsheikh","year":"2022","journal-title":"J Clin Pathol"},{"key":"pone.0338027.ref050","article-title":"Regulator of Chromosome Condensation (RCC1) a novel therapeutic target in pancreatic ductal adenocarcinoma drives tumor progression via the c-Myc-RCC1-Ran axis","author":"SF Bannoura","year":"2023","journal-title":"bioRxiv"},{"key":"pone.0338027.ref051","doi-asserted-by":"crossref","first-page":"620973","DOI":"10.3389\/fmolb.2020.620973","article-title":"Regulator of chromosome condensation 2 modulates cell cycle progression, tumorigenesis, and therapeutic resistance","volume":"7","author":"K Guo","year":"2021","journal-title":"Front Mol Biosci"},{"key":"pone.0338027.ref052","doi-asserted-by":"crossref","first-page":"107438","DOI":"10.1016\/j.pharmthera.2019.107438","article-title":"Drug resistance to targeted therapeutic strategies in non-small cell lung cancer","volume":"206","author":"W-J Liu","year":"2020","journal-title":"Pharmacol Ther"},{"issue":"5","key":"pone.0338027.ref053","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1159\/000443368","article-title":"Drug resistance to EGFR inhibitors in lung cancer","volume":"61","author":"O Tetsu","year":"2016","journal-title":"Chemotherapy"},{"issue":"4","key":"pone.0338027.ref054","doi-asserted-by":"crossref","first-page":"448","DOI":"10.2174\/1574892818666221026164940","article-title":"Gefitinib: an updated review of its role in the cancer management, its nanotechnological interventions, recent patents and clinical trials","volume":"18","author":"P Kumar","year":"2023","journal-title":"Recent Pat Anticancer Drug Discov"},{"issue":"5827","key":"pone.0338027.ref055","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1126\/science.1141478","article-title":"MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling","volume":"316","author":"JA Engelman","year":"2007","journal-title":"Science"},{"issue":"11","key":"pone.0338027.ref056","doi-asserted-by":"crossref","first-page":"2560","DOI":"10.1002\/ijc.28594","article-title":"The PI3K\/AKT pathway promotes gefitinib resistance in mutant KRAS lung adenocarcinoma by a deacetylase-dependent mechanism","volume":"134","author":"V Jeannot","year":"2014","journal-title":"Int J Cancer"},{"issue":"2","key":"pone.0338027.ref057","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1042\/BST20191055","article-title":"Targeted therapy and drug resistance in triple-negative breast cancer: the EGFR axis","volume":"48","author":"S Lev","year":"2020","journal-title":"Biochem Soc Trans"},{"key":"pone.0338027.ref058","doi-asserted-by":"crossref","first-page":"116909","DOI":"10.1016\/j.envres.2023.116909","article-title":"Synthesis and characterization of nanobiochar from rice husk biochar for the removal of safranin and malachite green from water","volume":"238","author":"S Aziz","year":"2023","journal-title":"Environ Res"},{"key":"pone.0338027.ref059","doi-asserted-by":"crossref","first-page":"113413","DOI":"10.1016\/j.biopha.2022.113413","article-title":"Application of nanotechnology to herbal antioxidants as improved phytomedicine: an expanding horizon","volume":"153","author":"Y Mishra","year":"2022","journal-title":"Biomed Pharmacother"},{"issue":"15","key":"pone.0338027.ref060","doi-asserted-by":"crossref","first-page":"3029","DOI":"10.3390\/nu14153029","article-title":"Neuronutraceuticals Combating Neuroinflammaging: Molecular Insights and Translational Challenges-A Systematic 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