{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T02:01:08Z","timestamp":1791856868214,"version":"4.3.4"},"reference-count":64,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2023,11,16]],"date-time":"2023-11-16T00:00:00Z","timestamp":1700092800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Innovation Team and Talents Cultivation Program"},{"name":"National Administration of Traditional Chinese Medicine","award":["ZYYCXTD-C-202005"],"award-info":[{"award-number":["ZYYCXTD-C-202005"]}]},{"name":"National Administration of Traditional Chinese Medicine","award":["81874368"],"award-info":[{"award-number":["81874368"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Breast cancer is a common malignancy in women. More than 90% of breast cancer deaths are caused by metastasis. Epimedii Folium (EF) is a commonly used herb with anti-tumor benefits, but its underlying mechanisms and active components for breast cancer prevention are little understood. This study assessed the therapeutic role of Icariside I (ICS I) in Epimedium flavonoids (EF) on lung metastasis of breast cancer, including the underlying mechanism.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Western blot, RT-qPCR, wound healing assay, colony formation assay, and flow cytometry were used to investigate the inhibition of breast cancer cells growth and migration by EF and ICS I through disrupting the IL-6\/STAT3 pathway. Combined with 4T1 breast cancer model in mice, Western blot, RT-qPCR, Hematoxylin and Eosin staining, immunohistochemistry were used to evaluate the therapeutic role of ICS I in proliferation, apoptosis, invasion, and metastasis of breast cancer.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key findings<\/jats:title>\n                    <jats:p>EF can inhibit STAT3 phosphorylation and reduce the colony formation and migration of breast cancer cells. Detecting the active ingredients in EF, we found ICS I can reduce the activation of STAT3 in 4T1 breast cancer cells, impair colony formation and migration. Moreover, ICS I induced cells G1 phase arrest and modulated Cyclin D1, CDK4, bcl-2, and bax to inhibit proliferation and survival of breast cancer cells. Similarly, the in vivo studies demonstrated that ICS I significantly suppressed tumor development and lung metastasis in the 4T1 mouse model. Tumor cells in vehicle group were arranged in a spoke-like pattern with obvious heterogeneity, and multinucleated tumor giant cells were seen. But, the tumor cells in the ICS I group were disorganized and necrotic lysis was seen in some areas. In ICS I-treated group, tumors\u2019 STAT3 phosphorylation level, IL-6, Cyclin D1, CDK4, bcl-2, and vimentin expression were downregulated, bax and cleaved caspase 3 expression were upregulated. In the lung tissue, we could find less metastasis of breast cancer cells and less lung injury in the ICS I group. Besides, the expression of metastasis-related genes MMP9 and vimentin was decreased in the lung tissue of ICS I group.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings suggest that ICS I can inhibit breast cancer proliferation, apoptosis, invasion and metastasis probably via targeting IL-6\/STAT3 pathway. Therefore, ICS I has the potential to become an innovative therapeutic candidate to breast cancer prevention and treatment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jpp\/rgad103","type":"journal-article","created":{"date-parts":[[2023,10,23]],"date-time":"2023-10-23T16:46:49Z","timestamp":1698079609000},"page":"499-513","source":"Crossref","is-referenced-by-count":22,"title":["Icariside I reduces breast cancer proliferation, apoptosis, invasion, and metastasis probably through inhibiting IL-6\/STAT3 signaling pathway"],"prefix":"10.1093","volume":"76","author":[{"given":"Manting","family":"Hou","sequence":"first","affiliation":[{"name":"Department of Hepatology, The Fifth Medical Center of Chinese PLA General Hospital , Beijing 100039 ,","place":["China"]},{"name":"China Military Institute of Chinese Materia, The Fifth Medical Center of Chinese PLA General Hospital , Beijing 100039 ,","place":["China"]},{"name":"School of Traditional Chinese Medicine, Southern Medical 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Fifth Medical Center of Chinese PLA General Hospital , Beijing 100039 ,","place":["China"]},{"name":"China Military Institute of Chinese Materia, The Fifth Medical Center of Chinese PLA General Hospital , Beijing 100039 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jincai","family":"Wen","sequence":"additional","affiliation":[{"name":"Department of Hepatology, The Fifth Medical Center of Chinese PLA General Hospital , Beijing 100039 ,","place":["China"]},{"name":"China Military Institute of Chinese Materia, The Fifth Medical Center of Chinese PLA General Hospital , Beijing 100039 ,","place":["China"]},{"name":"School of Traditional Chinese Medicine, Southern Medical University , Guangzhou 510515 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Kan","sequence":"additional","affiliation":[{"name":"Department of Hepatology, The Fifth Medical Center of Chinese PLA General Hospital , Beijing 100039 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