{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T15:56:01Z","timestamp":1790006161488,"version":"4.0.1"},"reference-count":35,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2013,7,26]],"date-time":"2013-07-26T00:00:00Z","timestamp":1374796800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Tamoxifen resistance remains to be a huge obstacle in the treatment of hormone-dependent breast cancer, and this therefore highlights the dire need to explore the underlying mechanisms. The epithelial-mesenchymal transition (EMT) is a molecular process through which an epithelial cell transfers into a mesenchymal phenotype. Roles of EMT in embryo development, cancer invasion and metastasis have been extensively reported. Herein, we established tamoxifen-resistant MCF-7\/TR breast cancer cells and showed that MCF-7\/TR cells underwent EMT driven by enhanced endogenous  TGF-\u03b2\/Smad signaling. Ectopic supplement of TGF-\u03b2 promoted in MCF-7 cells a mesenchymal and resistant phenotype. In parallel, we demonstrated that resveratrol was capable of synergizing with tamoxifen and triggering apoptosis in MCF-7\/TR cells.  Further Western blot analysis indicated that the chemosensitizing effects of resveratrol were conferred with its modulation on endogenous TGF-\u03b2 production and Smad phosphorylation. In particular, 50 \u03bcM resveratrol had minor effects on MCF-7\/TR cell proliferation, but could significantly attenuate endogenous TGF-\u03b2 production and the Smad pathway, ultimately leading to reversion of EMT. Collectively, our study highlighted distinct roles of EMT in tamoxifen resistance and resveratrol as a potential agent to overcome acquired tamoxifen resistance. The molecular mechanism of resveratrol chemosensitizing effects is, at least in part, TGF-\u03b2\/Smad-dependent.<\/jats:p>","DOI":"10.3390\/ijms140815655","type":"journal-article","created":{"date-parts":[[2013,7,26]],"date-time":"2013-07-26T22:13:15Z","timestamp":1374876795000},"page":"15655-15668","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":63,"title":["Resveratrol Sensitizes Tamoxifen in Antiestrogen-Resistant Breast Cancer Cells with Epithelial-Mesenchymal  Transition Features"],"prefix":"10.3390","volume":"14","author":[{"given":"Xiao-Peng","family":"Shi","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shan","family":"Miao","sequence":"additional","affiliation":[{"name":"Institute of Materia Medica, Fourth Military Medical University, Xi'an 710032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yin","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Public Health, Fourth Military Medical University, Xi'an 710032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Fang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua-Zhao","family":"Ma","sequence":"additional","affiliation":[{"name":"Outpatient Department, Institute of Armored Force, Bengbu 233050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hai-Li","family":"Xin","sequence":"additional","affiliation":[{"name":"Surgery Pharmacy of Department of Pharceutical Care, General Hospital of PLA,  Beijing 100853, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ai-Dong","family":"Wen","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2013,7,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"225","DOI":"10.3322\/caac.20006","article-title":"Cancer statistics, 2009","volume":"59","author":"Jemal","year":"2009","journal-title":"CA Cancer J. 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