{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T11:32:48Z","timestamp":1780918368199,"version":"3.54.1"},"reference-count":82,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T00:00:00Z","timestamp":1753833600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of University and Research (MUR)","award":["E83C22002040005"],"award-info":[{"award-number":["E83C22002040005"]}]},{"name":"University Scientific Research Projects 2021","award":["E83C22002040005"],"award-info":[{"award-number":["E83C22002040005"]}]},{"name":"Research and Innovation Projects (PON)","award":["E83C22002040005"],"award-info":[{"award-number":["E83C22002040005"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: During the repair of a wounded epithelium, keratinocytes become invasive via the epithelial-to-mesenchymal transition (EMT) process. Usually temporary and controlled, EMT persists in a chronically inflamed epithelium and is exacerbated in epithelial dysplasia and dysregulated in invasive carcinomas. Here we investigated the effects that IL-1 beta, IL-6, and IL-8, inflammatory cytokines expressed in specimens from OPMDs and OSCCs, have on NOKs and OSCC cells. Methods: AKT activation and EMT induction were assessed along with cellular invasiveness. Results: IL-1 beta, IL-6, and IL-8 induced EMT in NOKs, ex novo conferring them invasive capacity. The same cytokines exacerbated the constitutive EMT and invasiveness of OSCC cells. Since these phenomena were accompanied by AKT activation, we tested whether they could be influenced by RTV, a long-used anti-HIV drug that was previously found to block the activation of human AKT and exert antitumor effects. We observed that therapeutic amounts of RTV counteract all the above-mentioned tumorigenic activities of ILs. Finally, consistent with the key role that AKT and EMT play in OSCC radio-resistance, RTV increased OSCC cells\u2019 sensitivity to therapeutic doses of ionizing radiation. Conclusions: These preliminary in vitro findings encourage the use of RTV to prevent the malignant evolution of OPMDs, reduce the risk of OSCC metastasis, and improve the outcomes of anti-OSCC radiotherapy.<\/jats:p>","DOI":"10.3390\/cancers17152519","type":"journal-article","created":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T14:00:41Z","timestamp":1753884041000},"page":"2519","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["The HIV Protease Inhibitor Ritonavir Reverts the Mesenchymal Phenotype Induced by Inflammatory Cytokines in Normal and Tumor Oral Keratinocytes to an Epithelial One, Increasing the Radiosensitivity of Tumor Oral Keratinocytes"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7007-4238","authenticated-orcid":false,"given":"Silvia","family":"Pomella","sequence":"first","affiliation":[{"name":"Department of Clinical Sciences and Translational Medicine, University of Rome Tor Vergata, 00133 Rome, Italy"},{"name":"Department of Hematology and Oncology, Cell and Gene Therapy, Bambino Ges\u00f9 Children\u2019s Hospital, Istituto di Ricovero e Cura a Carattere Scientifico, 00146 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3202-2349","authenticated-orcid":false,"given":"Lucrezia","family":"D\u2019Archivio","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology, Cell and Gene Therapy, Bambino Ges\u00f9 Children\u2019s Hospital, Istituto di Ricovero e Cura a Carattere Scientifico, 00146 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2919-676X","authenticated-orcid":false,"given":"Matteo","family":"Cassandri","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology, Cell and Gene Therapy, Bambino Ges\u00f9 Children\u2019s Hospital, Istituto di Ricovero e Cura a Carattere Scientifico, 00146 Rome, Italy"},{"name":"Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3013-4504","authenticated-orcid":false,"given":"Francesca Antonella","family":"Aiello","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology, Cell and Gene Therapy, Bambino Ges\u00f9 Children\u2019s Hospital, Istituto di Ricovero e Cura a Carattere Scientifico, 00146 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7118-5186","authenticated-orcid":false,"given":"Ombretta","family":"Melaiu","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences and Translational Medicine, University of Rome Tor Vergata, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0588-3039","authenticated-orcid":false,"given":"Francesco","family":"Marampon","sequence":"additional","affiliation":[{"name":"Department of Radiological Oncological and Pathological Sciences, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9408-7711","authenticated-orcid":false,"given":"Rossella","family":"Rota","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology, Cell and Gene Therapy, Bambino Ges\u00f9 Children\u2019s Hospital, Istituto di Ricovero e Cura a Carattere Scientifico, 00146 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3423-4852","authenticated-orcid":false,"given":"Giovanni","family":"Barillari","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences and Translational Medicine, University of Rome Tor Vergata, 00133 Rome, Italy"},{"name":"Departmental Faculty of Medicine, Saint Camillus International University of Health and Medical Sciences, 00131 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Pomella, S., Melaiu, O., Cifaldi, L., Bei, R., Gargari, M., Campanella, V., and Barillari, G. 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