文献类型：期刊文献

英文题名：Dictamnine Inhibits WNT Pathway and EMT Progression in Prostate Cancer and Remodels the Tumor Microenvironment

作者：He, Han[1];Zhou, Chuan[2];Wang, Chao[3];Wang, Jia[4];Hu, Hongde[1];Yang, Jie[1];Zhou, Fenghai[1]

第一作者：He, Han

通信作者：Zhou, FH[1]

机构：[1]Lanzhou Univ, Clin Med Coll 1, Lanzhou 730000, Peoples R China;[2]Sichuan Prov Peoples Hosp, Chengdu 610032, Peoples R China;[3]Shaanxi Prov Peoples Hosp, Xian 710068, Peoples R China;[4]Gansu Univ Chinese Med, Clin Med Coll 1, Lanzhou 730050, Peoples R China

第一机构：Lanzhou Univ, Clin Med Coll 1, Lanzhou 730000, Peoples R China

通信机构：[1]corresponding author), Lanzhou Univ, Clin Med Coll 1, Lanzhou 730000, Peoples R China.

年份：2026

卷号：18

期号：5

外文期刊名：CANCERS

收录：;Scopus(收录号：2-s2.0-105032667318);WOS:【SCI-EXPANDED(收录号:WOS:001713425800001)】；

基金：This research was funded by the National Key Research and Development Program of China (Grant No. 2022YFC2407305); the Internal Research Projects of Gansu Provincial Hospital (Grant Nos. 2024GSSYE-7 and 23GSSYD-12); and the Internal Research Project of The First Hospital of Lanzhou University (Grant No. ldyyyn2023-33).

语种：英文

外文关键词：prostate cancer; dictamnine; DKK1; WNT pathway; tumor microenvironment

摘要：Objective: This study investigated the anti-prostate cancer mechanism of dictamnine (DIC), focusing on its potential to reverse EMT via DKK1-mediated Wnt/beta-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's interaction with LRP6. This upregulation of DKK1 inhibits the Wnt/beta-catenin signaling pathway, downregulating downstream targets beta-catenin/c-Myc/Cyclin D1, and reverses epithelial-mesenchymal 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/beta-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/beta-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.