{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T03:36:34Z","timestamp":1789616194976,"version":"build-2803163510"},"reference-count":35,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T00:00:00Z","timestamp":1758758400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Colorectal cancer (CRC) represents the most prevalent malignancy within the gastrointestinal system, with metastatic cases comprising approximately 50% of all CRC diagnoses. While chemotherapy remains the cornerstone treatment for metastatic CRC, the emergence of chemoresistance has significantly limited the clinical efficacy of 5\u2010fluorouracil (5\u2010FU) and oxaliplatin\u2010based regimens. In this study, we systematically investigated the therapeutic potential of puerarin in CRC management, focusing on its antitumor properties and chemosensitization effects. Our findings demonstrate that puerarin exhibits significant antitumor activity both in vitro and in vivo, while also potentiating the therapeutic effects of 5\u2010FU and oxaliplatin through synergistic interactions. Mechanistically, we identified PTEN as a critical molecular target of puerarin, evidenced by the reversal of puerarin\u2010mediated effects upon PTEN knockdown. Further molecular characterization revealed that puerarin exerts its antitumor effects through PTEN\u2010mediated suppression of AKT activation and subsequent induction of apoptotic pathways. Importantly, we established that puerarin enhances CRC cell sensitivity to 5\u2010FU and oxaliplatin via modulation of the PTEN\/PI3K\/AKT signaling axis. These findings not only elucidate a novel molecular mechanism underlying puerarin's anti\u2010CRC activity but also provide a promising therapeutic strategy for overcoming chemoresistance in CRC treatment.<\/jats:p>","DOI":"10.1002\/jbt.70517","type":"journal-article","created":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T08:56:52Z","timestamp":1758790612000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Puerarin Enhances the Sensitivity of Colorectal Cancer to 5\u2010Fluorouracil and Oxaliplatin by Inhibiting the PTEN\/PI3K\/AKT Signaling Pathway"],"prefix":"10.1002","volume":"39","author":[{"given":"Xiaowei","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Pharmacy Xi'an Eighth Hospital Xian P.R. 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