{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T09:48:23Z","timestamp":1782899303671,"version":"3.54.5"},"reference-count":42,"publisher":"Wiley","issue":"21","license":[{"start":{"date-parts":[[2024,11,4]],"date-time":"2024-11-04T00:00:00Z","timestamp":1730678400000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81760674"],"award-info":[{"award-number":["81760674"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>5\u2010fluorouracil (5\u2010FU) is a preferred chemotherapeutic agent for the treatment of colon cancer. Nonetheless, its clinical effectiveness is frequently hampered by suboptimal therapeutic outcomes and the emergence of drug resistance. Therefore, there exists a pressing demand for novel therapeutic agents to circumvent chemoresistance. The pregnane X receptor (PXR) exerts a pivotal regulatory influence on the proliferation, invasion, and chemoresistance mechanisms in colon cancer. Activation of PXR drives up the transcription of the multidrug resistance gene (MDR1), thus prompting the expression of P\u2010glycoprotein (P\u2010gp) responsible for conferring tumour resistance. This study scrutinized the potential of Fengliao Changweikang (FLCWK) in augmenting the efficacy of 5\u2010FU in the management of colon cancer. To this end, we engineered colon cancer cells with varied levels of PXR expression via lentiviral transfection, subsequently validating the findings in nude mice. By means of MTT assays, flow cytometry apoptosis analysis, Western blotting and immunofluorescence, we probed into the prospective impacts of FLCWK and 5\u2010FU on cellular viability and resistance. Our results revealed that while upregulation of PXR amplified the therapeutic benefits in colon cancer treatment, it concurrently heightened resistance levels. FLCWK demonstrated a capacity to reduce P\u2010gp expression, with the combined administration of FLCWK and 5\u2010FU effectively reversing resistance mechanisms. Furthermore, activation of PXR was found to impede the IL\u20106\/STAT3 signalling pathway. In an effort to mimic the development of colon cancer, we established an azomethane oxide (AOM)\/ dextran sodium sulfate (DSS) mouse model, showing that FLCWK bolstered the inhibitory effects of 5\u2010FU, impeding the progression of colon cancer. In summation, our findings point towards the potential of FLCWK in the treatment of colon cancer, particularly in strengthening the therapeutic efficacy of 5\u2010FU in the prevention and control of the disease.<\/jats:p>","DOI":"10.1111\/jcmm.70185","type":"journal-article","created":{"date-parts":[[2024,11,4]],"date-time":"2024-11-04T18:20:04Z","timestamp":1730744404000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["The combination of <scp>FLCWK<\/scp> with 5\u2010<scp>FU<\/scp> inhibits colon cancer and multidrug resistance by activating <scp>PXR<\/scp> to suppress the <scp>IL<\/scp>\u20106\/<scp>STAT3<\/scp> pathway"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2217-0708","authenticated-orcid":false,"given":"Lifan","family":"Zhong","sequence":"first","affiliation":[{"name":"School of Hainan Provincial Drug Safety Evaluation Research Center Hainan Medical University  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