{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T10:02:20Z","timestamp":1790935340916,"version":"4.1.0"},"reference-count":36,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2022,6,21]],"date-time":"2022-06-21T00:00:00Z","timestamp":1655769600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Oral Diseases"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Oral tongue squamous cell carcinoma (OTSCC) frequently harbors non\u2010functional p53 and depends on G2\/M checkpoint mediated by WEE1. WEE1 suppression has been identified as a promising anti\u2010tumor strategy. This study investigated the capacity of WEE1 kinase inhibitor (MK\u20101775) and its underlying mechanisms in enhancing radiation responses of OTSCC cells in vitro.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and methods<\/jats:title><jats:p>WEE1 kinase expression and its downstream target (CDK1) were investigated in OTSCC versus normal oral tissue. A synergistic combination of MK\u20101775 with radiation on OTSCC cell lines with different p53 statuses was assessed by viability assay. The radio\u2010sensitizing effects of MK\u20101775 on apoptosis, cell cycle, DNA damage, and mitotic entry were also determined.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Irradiation enhanced CDK1 expression in all tested cell lines, though the effect was far more pronounced in p53 mutated cell lines. MK\u20101775 exhibited inhibitory effects against the survival of all cell lines and enhanced their response to the radiation. These effects were strongly elicited by induction of apoptosis and lethal mitosis, but less likely by abrogation of radiation\u2010induced G2 arrest.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These results demonstrate the efficacy of MK\u20101775 in enhancing the radiation effect on OTSCC in vitro associated with a significant apoptotic death rate, identifying WEE1 inhibitor as a potent radiosensitizer in OTSCC irrespective of p53 mutational status.<\/jats:p><\/jats:sec>","DOI":"10.1111\/odi.14269","type":"journal-article","created":{"date-parts":[[2022,6,8]],"date-time":"2022-06-08T02:09:25Z","timestamp":1654654165000},"page":"2640-2649","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["<scp>WEE1<\/scp> kinase inhibitor <scp>MK<\/scp>\u20101775 sensitizes oral tongue squamous cell carcinoma cells to radiation irrespective of <scp>TP53<\/scp> status"],"prefix":"10.1111","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2692-0142","authenticated-orcid":false,"given":"Aisha Hussein","family":"Al\u2010Jamaei","sequence":"first","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery and Oral Pathology Amsterdam UMC\u2010location VUmc\/Academic Centre for Dentistry Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan G. 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Ramadugula","family":"Subramanyam","sequence":"additional","affiliation":[{"name":"Department of OMFS and Diagnostic Sciences, College of Dentistry King Faisal University  Al Hofuf Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tymour","family":"Forouzanfar","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery and Oral Pathology Amsterdam UMC\u2010location VUmc\/Academic Centre for Dentistry Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Sminia","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Amsterdam UMC Vrije Universiteit Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Behrouz Zandieh","family":"Doulabi","sequence":"additional","affiliation":[{"name":"Department of Oral Cell Biology Academic Centre for Dentistry Amsterdam\u2010University of Amsterdam and 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