{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T12:21:25Z","timestamp":1784204485730,"version":"3.55.0"},"reference-count":39,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,7,3]],"date-time":"2025-07-03T00:00:00Z","timestamp":1751500800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004479","name":"Natural Science Foundation of Jiangxi Province","doi-asserted-by":"publisher","award":["20232BAB206153"],"award-info":[{"award-number":["20232BAB206153"]}],"id":[{"id":"10.13039\/501100004479","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Kaohsiung J of Med Scie"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Rhaponitin (Rha) possesses anti\u2010tumor activity and mediates the transcriptional activity of hypoxia\u2010inducible factor (HIF)\u20101\u03b1 that affects cisplatin (Cis) resistance. However, whether Rha can lessen Cis resistance in tongue squamous cell carcinoma (TSCC) by mediating HIF\u20101\u03b1 activity is unclear. Cis\u2010resistant SCC9 (SCC9\u2010CisR) cells were treated with Cis, Rha, or Cis plus Rha to explore the effect of Rha on Cis resistance using a cell counting kit\u20108, flow cytometry, and tumor sphere formation assays. Stemness markers CD44 and SOX2 and HIF\u20101\u03b1 mRNA levels were detected by quantitative PCR. The GSE115119 database and plugin iRegulon were employed to select target genes mediated by HIF\u20101\u03b1. Protein levels of HIF\u20101\u03b1, monocarboxylate transporter 4 (MCT4), and the Wnt\/\u03b2\u2010catenin pathway were measured by western blot. Subcutaneous xenograft models were constructed to explore the efficacy of Rha in combating Cis resistance. Rha repressed the growth and stemness of SCC9\u2010CisR cells in\u00a0vitro and in\u00a0vivo. HIF\u20101\u03b1 protein levels were markedly elevated in SCC9\u2010CisR cells, yet Rha treatment attenuated the transcriptional activity of HIF\u20101\u03b1 but not HIF\u20101\u03b1 mRNA levels. Rha plus Cis repressed the viability and stemness of SCC9\u2010CisR cells, but not HIF\u20101\u03b1\u2010knockdown SCC9\u2010CisR cells, compared with Cis alone. Rha\u2010induced stemness inhibition and apoptosis in SCC9\u2010CisR cells were overridden after HIF\u20101\u03b1 overexpression. Rha inhibited the Wnt\/\u03b2\u2010catenin signaling by regulating the HIF\u20101\u03b1\/MCT4 axis. In conclusion, Rha reduced cell stemness and enhanced Cis sensitivity in TSCC, which was achieved possibly via suppressing the Wnt\/\u03b2\u2010catenin signaling through mediation of the HIF\u20101\u03b1\/MCT4 axis.<\/jats:p>","DOI":"10.1002\/kjm2.70069","type":"journal-article","created":{"date-parts":[[2025,7,3]],"date-time":"2025-07-03T12:39:55Z","timestamp":1751546395000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Rhaponitin Reverses Cisplatin Resistance and Impairs Cancer Stemness Through\n                    <scp>HIF<\/scp>\n                    \u20101\u03b1\/\n                    <scp>MCT4<\/scp>\n                    \/Wnt Pathway in Tongue Squamous Cell Carcinoma"],"prefix":"10.1002","volume":"41","author":[{"given":"Yuan","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine  Nanchang Jiangxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao\u2010Wen","family":"Wan","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine  Nanchang Jiangxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine  Nanchang Jiangxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine  Nanchang Jiangxi 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