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Enterolactone (ENL) has previously been reported to inhibit ovarian cancer in positive correlation with THBS1 expression, but the involved molecular events remain unknown. In this study, we looked into interactions between ENL and\n THBS1<\/jats:ext-link>\n to elucidate the mechanisms underlining their joint inhibitory effects on ovarian cancer.\n <\/jats:p>\n <\/jats:sec>\n \n Experimental Approach<\/jats:title>\n We observed the suppressive effect of ENL on ovarian cancer cells by cell counting kit\u20108, wound healing, transwell, western blot and immunohistochemistry assays. The binding of ENL to THSB1 was assessed by molecular docking and microscale thermophoresis assays. Inhibition of malignant angiogenesis by ENL was inspected by tube formation assay and zebrafish experiment. The in vivo anticancer abilities of ENL were investigated by xenograft and allograft ovarian cancer animal models, and the fecal microbiota was analysed by metagenomics.<\/jats:p>\n <\/jats:sec>\n \n Key Results<\/jats:title>\n \n This study demonstrated potent inhibitory effects of ENL on ovarian cancer by both in vitro and in vivo experiments. Analysis of 61 clinical samples showed a correlation between poor prognosis and low THBS1 expression. ENL affected the expression of THBS1 and other proteins such as\n CD36<\/jats:ext-link>\n . ENL through binding with the 3TSR domain of THBS1 inhibited malignant angiogenesis and suppressed cancer progression. ENL administration could also ameliorate gut dysbacteriosis.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Implications<\/jats:title>\n ENL has potent inhibitory effects on ovarian cancer and suppresses malignant angiogenesis by binding to THBS1\u20103TSR. ENL ameliorates gut dysbacteriosis.<\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/bph.70327","type":"journal-article","created":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T05:36:38Z","timestamp":1770874598000},"page":"2837-2856","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Enterolactone and THBS1\u20103TSR synergistically inhibit ovarian cancer and suppress angiogenesis in the tumour microenvironment"],"prefix":"10.1111","volume":"183","author":[{"given":"Caiji","family":"Lin","sequence":"first","affiliation":[{"name":"Genomics Research Center (Key Laboratory of Gut Microbiota and Pharmacogenomics of Heilongjiang Province, State\u2010Province Key Laboratory of Biomedicine\u2010Pharmaceutics of China), College of Pharmacy Harbin Medical University Harbin China"},{"name":"National Key Laboratory of Frigid Zone Cardiovascular Diseases Harbin Medical University Harbin China"},{"name":"Harbin Medical University\u2010University of Calgary Cumming School of Medicine Centre for Infection and Genomics Harbin Medical University Harbin China"},{"name":"Department of Nephrology, Institute of Nephrology 2nd Affiliated Hospital of Hainan Medical University Haikou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiaxing","family":"Wang","sequence":"additional","affiliation":[{"name":"Genomics Research Center (Key Laboratory of Gut Microbiota and Pharmacogenomics of Heilongjiang Province, State\u2010Province Key Laboratory of Biomedicine\u2010Pharmaceutics of China), College of Pharmacy Harbin Medical University Harbin China"},{"name":"National Key Laboratory of Frigid Zone Cardiovascular Diseases Harbin Medical University Harbin China"},{"name":"Harbin Medical University\u2010University of Calgary Cumming School of Medicine Centre for Infection and Genomics Harbin Medical University Harbin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuhui","family":"Chai","sequence":"additional","affiliation":[{"name":"Genomics Research Center (Key Laboratory of Gut Microbiota and Pharmacogenomics of Heilongjiang Province, State\u2010Province Key Laboratory of Biomedicine\u2010Pharmaceutics of China), College of Pharmacy Harbin Medical University Harbin China"},{"name":"National Key Laboratory of Frigid Zone Cardiovascular Diseases Harbin Medical University Harbin China"},{"name":"Harbin Medical University\u2010University of Calgary Cumming School of Medicine Centre for Infection and Genomics Harbin Medical University Harbin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Yan","sequence":"additional","affiliation":[{"name":"Genomics Research Center (Key Laboratory of Gut Microbiota and Pharmacogenomics of Heilongjiang Province, State\u2010Province Key Laboratory of Biomedicine\u2010Pharmaceutics of China), College of Pharmacy Harbin Medical University Harbin China"},{"name":"National Key Laboratory of Frigid Zone Cardiovascular Diseases Harbin Medical University Harbin China"},{"name":"Harbin Medical University\u2010University of Calgary Cumming School of Medicine Centre for Infection and Genomics Harbin Medical University Harbin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danli","family":"Cao","sequence":"additional","affiliation":[{"name":"Genomics Research Center (Key Laboratory of Gut Microbiota and Pharmacogenomics of Heilongjiang Province, State\u2010Province Key Laboratory of Biomedicine\u2010Pharmaceutics of China), College of Pharmacy Harbin Medical University Harbin China"},{"name":"National Key Laboratory of Frigid Zone Cardiovascular Diseases Harbin Medical University Harbin China"},{"name":"Harbin Medical University\u2010University of Calgary Cumming School of Medicine Centre for Infection and Genomics Harbin Medical University Harbin 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