J Ethnopharmacol
Department of Integrative Chinese and Western Medicine, Union Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, 1277 Liberation Avenue, 430022, Wuhan City, China. Electronic address:
Published: February 2025
Ethnopharmacological Relevance: Wu Mei Wan (WMW) is a traditional Chinese herbal formula with a long-standing history in Chinese medicine, valued for its therapeutic properties. However, its potential anti-cancer effects, especially against colorectal cancer (CRC), have not been fully elucidated.
Aim Of The Study: This study aims to investigate the effects of WMW on colorectal cancer stemness and to elucidate the underlying molecular mechanisms, focusing on the modulation of Sox9 expression via the JAK2/STAT3 signaling pathway.
Materials And Methods: WMW was prepared and analyzed using UPLC-MS to identify their main components. To study the therapeutic effects of WMW, AOM/DSS-induced CRC mouse models were established. A comprehensive suite of experimental techniques, including in vivo imaging, cell culture, transfection, CCK-8 assays, colony formation assays, wound healing assays, cell migration assays, Western blotting, dot blot analysis, RT-qPCR, immunohistochemistry, cell transcriptome sequencing, and gene set enrichment analysis, were utilized to explore the pharmacological effects and mechanisms of WMW.
Results: WMW significantly inhibited CRC cell viability, proliferation, invasion, and migration in vitro. Mechanistically, WMW suppressed CRC stemness by downregulating Sox9 expression through the JAK2/STAT3 signaling pathway. Additionally, the regulation of methylation and demethylation mediated by TET1 and DNMT3a expression was directly associated with the JAK2/STAT3 pathway's modulation of Sox9 expression. In vivo, WMW treatment attenuated CRC progression and metastasis with minimal toxicity.
Conclusion: These findings suggest that WMW exerts potent anti-CRC stemness effects by regulating Sox9 via the JAK2/STAT3 signaling pathway, underscoring its potential as a promising therapeutic agent for CRC treatment.
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http://dx.doi.org/10.1016/j.jep.2024.118998 | DOI Listing |
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