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The use of oxaliplatin (L\u2010OHP) as a first\u2010line treatment for CRC is limited due to chemoresistance. Growing evidence have revealed that the existence of cancer stem\u2010like cells (CSLCs) is one of the important reasons for drug resistance and recurrence of cancers. Dihydroartemisinin (DHA), a derivative of artemisinin, has showed anticancer effects on a variety of malignancies, in addition to its antimalarial effects. However, the effect and mechanism of DHA on CSLCs and chemosensitivity in CRC cells remains unclear. In this study, we found that DHA inhibited cell viability in HCT116 and SW620 cells. Moreover, DHA decreased cell clonogenicity, and improved L\u2010OHP sensitivity. Furthermore, DHA treatment attenuated tumor sphere formation, and the expressions of stem cell surface marker (CD133 and CD44) and stemness\u2010associated transcription factor (Nanog, c\u2010Myc, and OCT4). Mechanistically, the present findings showed that DHA inhibited of AKT\/mTOR signaling pathway. The activation of AKT\/mTOR signaling reversed DHA\u2010decreased cell viability, clonogenicity, L\u2010OHP resistance, tumor sphere, and expressions of stemness\u2010associated protein in CRC. The inhibitory effect of DHA on tumorigenicity of CRC cells has also been demonstrated in BALB\/c nude mice. In conclusion, this study revealed that DHA inhibited CSLCs properties in CRC via AKT\/mTOR signaling, suggesting that DHA may be used as a potential therapeutic agent for CRC.<\/jats:p>","DOI":"10.1002\/ddr.22067","type":"journal-article","created":{"date-parts":[[2023,5,3]],"date-time":"2023-05-03T05:34:17Z","timestamp":1683092057000},"page":"988-998","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Dihydroartemisinin inhibited stem cell\u2010like properties and enhanced oxaliplatin sensitivity of colorectal cancer via AKT\/mTOR signaling"],"prefix":"10.1002","volume":"84","author":[{"given":"Yujun","family":"Wang","sequence":"first","affiliation":[{"name":"School of Pharmacy Chengdu Medical College Chengdu China"},{"name":"The Second Affiliated Hospital of Chengdu Medical College China National Nuclear Corporation 416 Hospital  Chengdu 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