{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T09:13:15Z","timestamp":1783674795594,"version":"3.55.0"},"reference-count":45,"publisher":"Wiley","issue":"13","license":[{"start":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T00:00:00Z","timestamp":1775174400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T00:00:00Z","timestamp":1775174400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100005047","name":"Natural Science Foundation of Liaoning Province","doi-asserted-by":"publisher","award":["2023\u2010MHLS\u2010286"],"award-info":[{"award-number":["2023\u2010MHLS\u2010286"]}],"id":[{"id":"10.13039\/501100005047","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Purpose<\/jats:title>\n                    <jats:p>\n                      Previous studies have found that activation of the \u03b3\u2010secretase\/NICD\u2010PXR\/Notch pathway can induce Taxol resistance in triple\u2010negative breast cancer (TNBC) to limit its therapeutic effect. Accordingly, inhibition of the \u03b3\u2010secretase\/Notch pathway maybe an effective strategy to enhance Taxol chemosensitivity in TNBC. We have already found that cimigenoside (CG), the active ingredient of\n                      <jats:italic>Cimicifuga dahurica<\/jats:italic>\n                      (Turcz.) Maxim, can inhibit \u03b3\u2010secretase activity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>The dynamic interaction between the natural \u03b3\u2010secretase inhibitor CG and \u03b3\u2010secretase catalytic core presenilin\u20101 (PSEN\u20101) was revealed by molecular dynamics simulations and in vitro enzyme activity experiments. The biological characterisation and in vivo role of CG in increasing Taxol sensitivity of TNBC were investigated. The regulatory effect of CG on the \u03b3\u2010secretase\/RBPJ\u2010PXR axis was studied through dual luciferase reporter gene assays, nuclear cytoplasmic separation experiments, and western blot assays.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>CG stably binds to the PSEN\u20101 protein cavity to inhibit \u03b3\u2010secretase activity. In vitro studies showed that CG significantly enhanced the inhibition of cell proliferation, migration and invasion, as well as the promotion of apoptosis of MDA\u2010MB\u2010231\/Taxol cells by Taxol. CG enhanced the inhibitory effect of Taxol on subcutaneous tumours and lung metastatic TNBC in vivo. Mechanistically, CG inhibited the transcriptional activity of RBPJ by targeting \u03b3\u2010secretase, interfered with the interaction between RBPJ and pregnane X receptor (PXR), down\u2010regulated the expression of PXR\u2010regulated metabolic enzymes and transport proteins, and enhanced the sensitivity of TNBC to Taxol.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Implications<\/jats:title>\n                    <jats:p>We show that CG enhances the chemical sensitivity of TNBC by regulating the \u03b3\u2010secretase\/RBPJ\u2010PXR axis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.70439","type":"journal-article","created":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T04:55:03Z","timestamp":1775278503000},"page":"3666-3684","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cimigenoside enhances Taxol chemosensitivity in triple\u2010negative breast cancer via the \u03b3\u2010secretase\/RBPJ\u2010PXR axis"],"prefix":"10.1111","volume":"183","author":[{"given":"Mei","family":"Feng","sequence":"first","affiliation":[{"name":"Department of Pathology and Pathophysiology, School of Basic Medical Sciences Shenyang Medical College  Shenyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology General Hospital of Northern Theater Command  Shenyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuo","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Pathology and Pathophysiology, School of Basic Medical Sciences Shenyang Medical College  Shenyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke\u2010Fan","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pathology and Pathophysiology, School of 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