{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T06:12:18Z","timestamp":1777961538457,"version":"3.51.4"},"reference-count":33,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T00:00:00Z","timestamp":1777852800000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>Accumulating evidence indicates that indirubin exerts inhibitory effects on prostate cancer (PCa) progression. However, the role and underlying mechanisms of indirubin in sensitizing PCa to docetaxel remain unclear. CCK\u20108 assays were initially used to determine the effect of indirubin on enhancing docetaxel sensitivity in PCa cells. Following this, the expression levels of circ\u2010Vav3 were quantified using quantitative real\u2010time PCR (RT\u2010qPCR) to evaluate its potential role in docetaxel resistance. Functional experiments, including flow cytometry\u2010based apoptosis analysis and Transwell migration\/invasion assays, were conducted to assess the impact of circ\u2010Vav3 modulation and indirubin treatment on cell viability and behavior in response to docetaxel. Rescue experiments were subsequently performed to further confirm the regulatory effect of indirubin on circ\u2010Vav3. Additionally, xenograft tumor models in nude mice were utilized to evaluate the therapeutic efficacy of indirubin in vivo. Mechanistic interactions between circ\u2010Vav3, miR\u2010204\u20105p, and MAPK1 were further investigated using RNA pulldown assays, luciferase reporter assays, and Western blot analyses. Indirubin enhanced the sensitivity of PCa cells to docetaxel by downregulating the expression of circ\u2010Vav3, which was found to be significantly upregulated in docetaxel\u2010resistant PCa cells. Silencing circ\u2010Vav3 effectively reversed this resistance, as evidenced by increased apoptosis, reduced cell migration and invasion, and decreased autophagic activity. Notably, indirubin treatment suppressed circ\u2010Vav3 expression and thereby restored docetaxel sensitivity both in vitro and in xenograft tumor models. Mechanistically, circ\u2010Vav3 acted as a competing endogenous RNA (ceRNA) by sponging miR\u2010204\u20105p, which led to the upregulation of the autophagy\u2010related kinase MAPK1. Inhibition of MAPK1 effectively suppressed autophagy and re\u2010sensitized docetaxel\u2010resistant PCa cells, further confirming the critical regulatory role of the circ\u2010Vav3\/miR\u2010204\u20105p\/MAPK1 signaling axis in mediating chemoresistance. Our findings demonstrate that circ\u2010Vav3 promotes docetaxel resistance in PCa by sponging miR\u2010204\u20105p and subsequently activating MAPK1\u2010mediated autophagy. Indirubin effectively restores chemosensitivity by targeting this regulatory pathway, offering a promising therapeutic strategy for overcoming chemoresistance in castration\u2010resistant prostate cancer (CRPC).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jbt.70884","type":"journal-article","created":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T05:41:07Z","timestamp":1777959667000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Indirubin Sensitizes Prostate Cancer to Docetaxel by Inhibiting Autophagy Through the circ\u2010Vav3\/miR\u2010204\u20105p\/MAPK1 Pathway"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-6842-5757","authenticated-orcid":false,"given":"Minghao","family":"Zheng","sequence":"first","affiliation":[{"name":"Department of Urology Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gan","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Urology Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Long","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Urology Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xian","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Urology Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine Nanjing 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China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuaiyu","family":"Niu","sequence":"additional","affiliation":[{"name":"Department of Urology Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanpei","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Urology Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Urology Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingyuan","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of 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