{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T17:26:37Z","timestamp":1793467597935,"version":"4.5.0"},"reference-count":47,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T00:00:00Z","timestamp":1772150400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFC2407305"],"award-info":[{"award-number":["2022YFC2407305"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Internal Research Projects of Gansu Provincial Hospital","award":["2024GSSYE-7"],"award-info":[{"award-number":["2024GSSYE-7"]}]},{"name":"Internal Research Projects of Gansu Provincial Hospital","award":["23GSSYD-12"],"award-info":[{"award-number":["23GSSYD-12"]}]},{"name":"Internal Research Project of The First Hospital of Lanzhou University","award":["ldyyyn2023-33"],"award-info":[{"award-number":["ldyyyn2023-33"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Objective: This study investigated the anti-prostate cancer mechanism of dictamnine (DIC), focusing on its potential to reverse EMT via DKK1-mediated Wnt\/\u03b2-catenin inhibition and modulate the tumor microenvironment. Methods: Cell viability, proliferation, migration, and invasion were assessed using CCK-8, colony formation, EdU, wound healing, and Transwell assays. Key targets were identified via transcriptomics and bioinformatics, and validated through molecular docking, co-immunoprecipitation, and cellular thermal shift assay. Protein expression was analyzed by Western blot. Gain\/loss-of-function and rescue experiments confirmed target roles. A subcutaneous xenograft model and immunohistochemistry were used for in vivo validation. Results: DIC suppresses prostate cancer malignancy in a concentration-dependent manner. The primary mechanism involves its direct binding to and stabilization of DKK1, which enhances DKK1\u2019s interaction with LRP6. This upregulation of DKK1 inhibits the Wnt\/\u03b2-catenin signaling pathway, downregulating downstream targets \u03b2-catenin\/c-Myc\/Cyclin D1, and reverses epithelial\u2013mesenchymal transition (EMT) markers. Additionally, DIC modulates key tumor microenvironment factors, including VEGF-A, MMP-9, IL-11, and CXCL-12. Overexpression of DKK1 mimics the antitumor effects of DIC, while knockdown of DKK1 attenuates them. In vivo, DIC inhibits tumor growth, an effect partly mediated through the DKK1\/\u03b2-catenin axis. Furthermore, DIC potently suppresses angiogenesis (reduced CD31+ staining) independently of DKK1. It also increases tumor-associated macrophage infiltration (elevated F4\/80+ cells) in a DKK1-independent manner. Conclusions: DIC exerts its core antitumor effects by targeting DKK1 to inhibit Wnt\/\u03b2-catenin signaling and EMT. Additionally, it independently suppresses angiogenesis and remodels the immune tumor microenvironment. This multi-level mechanism positions DIC as a promising lead compound for prostate cancer therapy.<\/jats:p>","DOI":"10.3390\/cancers18050771","type":"journal-article","created":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T17:05:16Z","timestamp":1772211916000},"page":"771","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Dictamnine Inhibits WNT Pathway and EMT Progression in Prostate Cancer and Remodels the Tumor Microenvironment"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-9508-4288","authenticated-orcid":false,"given":"Han","family":"He","sequence":"first","affiliation":[{"name":"The First Clinical Medical College of Lanzhou University, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuan","family":"Zhou","sequence":"additional","affiliation":[{"name":"Sichuan Provincial People\u2019s Hospital, Chengdu 610032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Wang","sequence":"additional","affiliation":[{"name":"Shaanxi Provincial People\u2019s Hospital, Xi\u2019an 710068, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Wang","sequence":"additional","affiliation":[{"name":"The First Clinical Medical College of Gansu University of Chinese Medicine, Lanzhou 730050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongde","family":"Hu","sequence":"additional","affiliation":[{"name":"The First Clinical Medical College of Lanzhou University, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Yang","sequence":"additional","affiliation":[{"name":"The First Clinical Medical College of Lanzhou University, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fenghai","family":"Zhou","sequence":"additional","affiliation":[{"name":"The First Clinical Medical College of Lanzhou University, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,27]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global Cancer Statistics 2022: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. 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