{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T05:36:09Z","timestamp":1777872969244,"version":"3.51.4"},"reference-count":44,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:00:00Z","timestamp":1777507200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Thailand Science research and Innovation Fund Chulalongkorn University"},{"name":"Ratchadapisek Somphot Fund for Postdoctoral Fellowship, Chulalongkorn University"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>Ivermectin (IVM), initially developed as an antiparasitic drug, has recently demonstrated notable anticancer activity in several malignancies, including breast cancer. Our previous work showed that IVM inhibited cell proliferation and invasion in breast cancer cells, primarily through modulation of the Wnt signaling pathway. Preliminary results further indicated that combining IVM with tamoxifen enhanced its antiproliferative effects in endocrine-resistant breast cancer cells, suggesting a potential role in overcoming drug resistance. To further clarify IVM\u2019s mechanism in the context of endocrine resistance, this study investigated its effects on estrogen receptor-positive (ER\u207a) and endocrine-resistant breast cancer cells. IVM significantly suppressed estrogen-induced proliferation and downregulated key resistance-associated markers, including ER and HER2. Additionally, IVM treatment markedly reduced ERK, a downstream effector linked to HER2 and TGF-\u03b2 signaling. This inhibition was accompanied by a decrease in phosphorylated SMAD2 (pSMAD2) within the TGF-\u03b2 pathway, while levels of SMAD4\u2014a factor associated with favorable prognosis in endocrine resistance\u2014were maintained. Collectively, these findings highlight IVM\u2019s potential as a repurposed therapeutic agent, with the dual capacity to prevent endocrine resistance in ER\u207a breast cancer and to enhance anti-hormonal therapies in resistant cases.<\/jats:p>","DOI":"10.1371\/journal.pone.0348260","type":"journal-article","created":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T17:47:57Z","timestamp":1777571277000},"page":"e0348260","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Ivermectin inhibits ER, HER2, and TGF-\u03b2 pathways in ER-positive and endocrine-resistant breast cancer 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