{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T05:11:57Z","timestamp":1780549917790,"version":"3.54.1"},"reference-count":40,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T00:00:00Z","timestamp":1764892800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008257","name":"Tarbiat Modares University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008257","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    This research investigates the effects of nano-curcumin on the expression of\n                    <jats:italic>Cyclin D1<\/jats:italic>\n                    and\n                    <jats:italic>DILA1<\/jats:italic>\n                    genes, as well as on the\n                    <jats:italic>PI3K\/AKT\/mTOR<\/jats:italic>\n                    pathway, in tamoxifen-sensitive and resistant MCF-7 breast cancer cell lines. The IC50 values were determined using the MTT assay. To establish tamoxifen-resistant MCF7 cells, a stepwise exposure to tamoxifen was conducted, gradually increasing the concentration to twice the IC50 dose. Following treatment with nano-curcumin, cell migration, proliferation, and apoptosis were evaluated using a wound healing assay and flow cytometry. Additionally, the impact of nano-curcumin on the\n                    <jats:italic>PI3K\/AKT\/mTOR and Cyclin D1<\/jats:italic>\n                    signaling pathways was analyzed via qRT-PCR and Western blot. Nano-curcumin treatment significantly inhibits cell proliferation, viability, and migration and promotes apoptosis in tamoxifen-sensitive and resistant MCF7 cell lines. qRT-PCR and Western blot analyses revealed reduced expression of\n                    <jats:italic>Cyclin D1, DILA1, NF-<\/jats:italic>\n                    \u03ba\n                    <jats:italic>B, PI3K, AKT, mTOR, VEGF<\/jats:italic>\n                    \u03b1,\n                    <jats:italic>MMP2<\/jats:italic>\n                    , and\n                    <jats:italic>BCL2<\/jats:italic>\n                    , along with increased levels of\n                    <jats:italic>PTEN, TIMP3, RECK<\/jats:italic>\n                    , and\n                    <jats:italic>BAX<\/jats:italic>\n                    . Our results indicate that nano-curcumin mitigates drug resistance by decreasing\n                    <jats:italic>DILA1<\/jats:italic>\n                    expression, which destabilizes Cyclin D1 protein and downregulates\n                    <jats:italic>PI3K\/AKT\/mTOR<\/jats:italic>\n                    pathway genes. Additionally, nano-curcumin induces apoptosis and inhibits migration. These findings suggest the nano-curcumin and tamoxifen combination may be a promising therapeutic strategy to overcome drug resistance in ER+ breast malignancies.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0335165","type":"journal-article","created":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T18:28:15Z","timestamp":1764959295000},"page":"e0335165","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["Nano-curcumin enhances the sensitivity of tamoxifen-resistant breast cancer cells via the Cyclin D1-DILA1 axis and the PI3K\/AKT\/mTOR pathway downregulation"],"prefix":"10.1371","volume":"20","author":[{"given":"Taraneh","family":"Givi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatemeh","family":"Mohajerani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zahra Moazezi","family":"Tehrankhah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3345-7595","authenticated-orcid":true,"given":"Mohammadjavad","family":"Karimi Taheri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maryam","family":"Amirahmadi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7066-0918","authenticated-orcid":true,"given":"Sadegh","family":"Babashah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2497-3152","authenticated-orcid":true,"given":"Majid","family":"Sadeghizadeh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,12,5]]},"reference":[{"issue":"3","key":"pone.0335165.ref001","first-page":"209","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"H Sung","year":"2021","journal-title":"CA Cancer J Clin"},{"issue":"3","key":"pone.0335165.ref002","first-page":"309","article-title":"Incidence and mortality of various cancers in Iran and compare to other countries: A review article","volume":"47","author":"B Farhood","year":"2018","journal-title":"Iran J Public Health"},{"key":"pone.0335165.ref003","doi-asserted-by":"crossref","first-page":"710286","DOI":"10.3389\/fonc.2021.710286","article-title":"CXCL9 Is a Potential Biomarker of Immune Infiltration Associated With Favorable Prognosis in ER-Negative Breast Cancer","volume":"11","author":"Y-K Liang","year":"2021","journal-title":"Front Oncol"},{"issue":"9793","key":"pone.0335165.ref004","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1016\/S0140-6736(11)60993-8","article-title":"Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomised trials","volume":"378","author":"Early Breast Cancer Trialists\u2019 Collaborative Group (EBCTCG)","year":"2011","journal-title":"Lancet"},{"issue":"1","key":"pone.0335165.ref005","doi-asserted-by":"crossref","first-page":"5513","DOI":"10.1038\/s41467-020-19349-w","article-title":"LncRNA DILA1 inhibits Cyclin D1 degradation and contributes to tamoxifen resistance in breast cancer","volume":"11","author":"Q Shi","year":"2020","journal-title":"Nat Commun"},{"key":"pone.0335165.ref006","doi-asserted-by":"crossref","unstructured":"Chang. 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