{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T07:18:50Z","timestamp":1787815130276,"version":"build-2784847793"},"reference-count":40,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["NSFC82360958"],"award-info":[{"award-number":["NSFC82360958"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["NSFC82560962"],"award-info":[{"award-number":["NSFC82560962"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004479","name":"Natural Science Foundation of Jiangxi Province","doi-asserted-by":"publisher","award":["20224ACB206039"],"award-info":[{"award-number":["20224ACB206039"]}],"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"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Tongue squamous cell carcinoma, the most aggressive subtype of oral squamous cell carcinoma, which is associated with high mortality, frequent recurrence, and early lymph\u2010node metastasis. Triptolide, a bioactive diterpenoid from\n                    <jats:italic>Tripterygium wilfordii<\/jats:italic>\n                    , exhibits broad anticancer activity. Although its inhibitory action on OSCC has been established, its specific molecular regulatory mechanisms in TSCC, a distinct and aggressive subtype, remain largely underexplored. The present study investigates the regulatory role of triptolide in the PI3K\u2013AKT signaling pathway, which is a critical axis intimately linked to tumor survival and metastasis. A network\u2010pharmacology workflow was used to intersect triptolide putative targets with TSCC\u2010related genes. Core hubs were identified with Cytoscape; KEGG and GO analyses highlighted the PI3K\u2013AKT axis as the top enriched pathway. Binding kinetics were quantified by molecular docking and surface plasmon resonance (SPR). Cellular assays (CCK\u20108, Transwell, wound\u2010healing, Western blot and immunofluorescence) validated the predictions. We retrieved 389 common targets and shortlisted eight key nodes (JUN, MAPK1, MAPK3, AKT1, TP53, BCL2, STAT3, MYC). SPR revealed high\u2010affinity binding of triptolide to AKT1 and PI3K. Functionally, triptolide dose\u2010dependently suppressed TSCC cell proliferation, invasion, and migration, downregulated PI3K\u2013AKT signaling proteins, and reduced the colocalization and phosphorylation levels of p\u2010PI3K and p\u2010AKT. This study is the first to demonstrate the pivotal role of the PI3K\u2013AKT signaling pathway in mediating the antitumor effects of triptolide in tongue squamous cell carcinoma. Our findings thereby provide a novel theoretical foundation for the development of traditional Chinese medicine\u2010based therapeutic strategies targeting this malignancy.\n                  <\/jats:p>","DOI":"10.1002\/kjm2.70283","type":"journal-article","created":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T06:44:34Z","timestamp":1787813074000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Triptolide Suppresses Tongue Squamous Cell Carcinoma Progression via\n                    <scp>PI3K<\/scp>\n                    \u2013\n                    <scp>AKT<\/scp>\n                    Pathway Inhibition: An Integrative Network Pharmacology and Experimental Validation Study"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-0204-2307","authenticated-orcid":false,"given":"Shan\u2010Shan","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Key Laboratory of Oral Diseases of Traditional Chinese Medicine Jiangxi University of Traditional Chinese Medicine  Nanchang China"},{"name":"School of Stomatology Nanchang University  Nanchang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-2827-0072","authenticated-orcid":false,"given":"Hong\u2010Cheng","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Key Laboratory of Oral Diseases of Traditional Chinese Medicine Jiangxi University of Traditional Chinese Medicine  Nanchang China"},{"name":"School of Stomatology Nanchang University  Nanchang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Key Laboratory of Oral Diseases of Traditional Chinese Medicine Jiangxi University of Traditional Chinese Medicine  Nanchang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9558-7534","authenticated-orcid":false,"given":"Yi\u2010Sen","family":"Shao","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Key Laboratory of Oral Diseases of Traditional Chinese Medicine Jiangxi University of Traditional Chinese Medicine  Nanchang China"},{"name":"School of Stomatology Nanchang University  Nanchang China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,26]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1002\/ame2.12367","article-title":"Towards System Genetics Analysis of Head and Neck Squamous Cell Carcinoma Using the Mouse Model, Cellular Platform, and Clinical Human Data","volume":"6","author":"Zohud O.","year":"2023","journal-title":"Animal Models and Experimental Medicine"},{"key":"e_1_2_8_3_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.oraloncology.2021.105451","article-title":"Overview of Oral Cavity Squamous Cell Carcinoma: Risk Factors, Mechanisms, and Diagnostics","volume":"121","author":"Chamoli A.","year":"2021","journal-title":"Oral Oncology"},{"key":"e_1_2_8_4_1","first-page":"229","article-title":"Global Cancer Statistics 2022: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"74","author":"Bray F.","year":"2024","journal-title":"CA: A Cancer Journal for Clinicians"},{"key":"e_1_2_8_5_1","doi-asserted-by":"crossref","first-page":"837","DOI":"10.2217\/fon.10.35","article-title":"Clinical, Pathological and Molecular Determinants in Squamous Cell Carcinoma of the Oral Cavity","volume":"6","author":"Al\u2010Swiahb J. 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