{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T23:19:19Z","timestamp":1788477559234,"version":"build-2803163510"},"reference-count":45,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T00:00:00Z","timestamp":1778803200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T00:00:00Z","timestamp":1778803200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2023YFC3503900"],"award-info":[{"award-number":["2023YFC3503900"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013115","name":"Zhejiang Provincial Program for the Cultivation of High-Level Innovative Health Talents","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013115","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Phytotherapy Research"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    <jats:italic>Atractylodes macrocephala<\/jats:italic>\n                    Koidz. has long been used for invigorating Qi and traditionally prescribed for cancer treatment by Chinese medicine practitioners. Atractylenolide I (ATI) is a major active component in\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>A. macrocephala<\/jats:italic>\n                    <\/jats:styled-content>\n                    and has inhibitory effects on various malignancies. Triple\u2010negative breast cancer (TNBC)\u2010related deaths are predominantly attributed to metastasis. However, the activity and mechanism of ATI on TNBC metastasis are unclear. Cell viability was detected by CCK\u20108 assay. Cell migration was determined by wound healing and transwell assays. The in\u00a0vivo experiment was performed in 4\u2009T1 spontaneous metastasis breast cancer nude mice. The mechanism was investigated by RNA\u2010seq analysis, and further verified by bioinformatics, qPCR, western blot, and siRNA transfection analysis. ATI inhibited the growth of 4TI cells. Additionally, ATI repressed the wound healing, invasion, and migration activities of 4TI and MDA\u2010MB\u2010231 cells at a lower concentration. In\u00a0vivo experiment revealed that while ATI (50\u2009mg\/kg) did not significantly inhibit tumor growth but markedly suppressed lung metastasis progression in a 4\u2009T1 spontaneous metastasis mouse model. RNA\u2010seq analysis of lung tissues showed that the extracellular matrix (ECM) signaling pathway was significantly suppressed by ATI. In addition, ATI inhibited the mRNA and protein levels of ECM\u2010related members (SPP1, MMP9, and COL1A1) in\u00a0vitro and in\u00a0vivo. Bioinformatics analysis revealed that the overexpression of SPP1 correlated with the poor prognosis of breast cancer patients. Furthermore, ATI inhibited ECM activator pyrintegrin\u2010induced wound healing. siRNA knockdown of SPP1 abolished ATI's inhibition on wound healing, cell migration, and expression of ECM\u2010related genes\/proteins in 4\u2009T1 cells. Molecular docking showed that ATI interacted with Trp\u2010106, Pro\u201044, and Leu\u201046 residues in SPP1 (\u22127.73\u2009kcal\/mol). Our findings suggest that ATI could suppress the lung metastasis of TNBC by inhibiting the SPP1\u2010mediated ECM signaling pathway.\n                  <\/jats:p>","DOI":"10.1002\/ptr.70385","type":"journal-article","created":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T12:03:51Z","timestamp":1778846631000},"page":"4660-4675","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Atractylenolide I Blocks Lung Metastasis of Triple\u2010Negative Breast Cancer by Inhibiting\n                    <scp>SPP1<\/scp>\n                    \u2010Mediated Extracellular Matrix Signaling Pathway"],"prefix":"10.1002","volume":"40","author":[{"given":"Qingling","family":"Wang","sequence":"first","affiliation":[{"name":"Zhejiang Provincial International S&amp;T Cooperation Base for Active Ingredients of Medicinal and Edible Plants and Health, Zhejiang Provincial Key TCM Laboratory for Chinese Resource Innovation and Transformation Institute of Chinese Medicine Resource Innovation and Quality Evaluation, School of Pharmaceutical Sciences, Jinhua Academy, Zhejiang Chinese Medical University  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxin","family":"Wang","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial International S&amp;T Cooperation Base for Active Ingredients of Medicinal and Edible Plants and Health, Zhejiang Provincial Key TCM Laboratory for Chinese Resource Innovation and Transformation Institute of Chinese Medicine Resource Innovation and Quality Evaluation, School of Pharmaceutical Sciences, Jinhua Academy, Zhejiang Chinese Medical University  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruiwen","family":"Yang","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial International S&amp;T Cooperation Base for Active Ingredients of Medicinal and Edible Plants and Health, Zhejiang Provincial Key TCM Laboratory for Chinese Resource Innovation and Transformation Institute of Chinese Medicine Resource Innovation and Quality Evaluation, School of Pharmaceutical Sciences, Jinhua Academy, Zhejiang Chinese Medical University  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Food Science, Fujian Agriculture and Forestry University  Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinmin","family":"Tu","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial International S&amp;T Cooperation Base for Active Ingredients of Medicinal and Edible Plants and Health, Zhejiang Provincial Key TCM Laboratory for Chinese Resource Innovation and Transformation Institute of Chinese Medicine Resource Innovation and Quality Evaluation, School of Pharmaceutical Sciences, Jinhua Academy, Zhejiang Chinese Medical University  Hangzhou 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