{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T13:53:32Z","timestamp":1787320412143,"version":"build-2736575974"},"reference-count":50,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007620","name":"Liaoning Provincial Education Department","doi-asserted-by":"publisher","award":["LJKFZ20220251"],"award-info":[{"award-number":["LJKFZ20220251"]}],"id":[{"id":"10.13039\/501100007620","id-type":"DOI","asserted-by":"publisher"}]},{"award":["LJKFZ20220251"],"award-info":[{"award-number":["LJKFZ20220251"]}],"id":[{"id":"https:\/\/ror.org\/0022v2454","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Nasopharyngeal carcinoma-associated malignant epithelial models remain useful for exploring integrin-related therapeutic strategies. In this study, we evaluated the antitumor activity and potential mechanisms of rRGD3mu, a recombinant peptide with a triple-RGD architecture. Using CNE2 cells as the primary experimental model, we evaluated cell viability, colony formation, migration, invasion, adhesion, apoptosis-related marker expression, and EMT-associated molecular changes. In vivo efficacy was assessed using a CNE2 cell-derived BALB\/c nude mouse xenograft model. rRGD3mu inhibited CNE2 cell viability, clonogenic growth, migration, invasion, and adhesion in a dose-dependent manner and suppressed xenograft tumor growth under the tested dosing schedule. Mechanistically, rRGD3mu promoted mitochondria-associated apoptosis, as indicated by an increased Bax\/Bcl-2 ratio and caspase-9\/3 activation, and modulated the expression of EMT-associated markers, including E-cadherin, N-cadherin, vimentin, and MMP2. Bioinformatic analysis and experimental validation suggested that ITGB1-containing integrin complexes might serve as important mediators and putative cellular engagement sites of rRGD3mu. rRGD3mu treatment reduced ITGB1 protein abundance and attenuated FAK\/AKT signaling. ITGB1 knockdown partially mimicked the effects of rRGD3mu and reduced the additional cellular response to rRGD3mu treatment, supporting the substantial contribution of ITGB1-associated signaling. These findings provide preliminary mechanistic evidence that rRGD3mu suppresses malignant phenotypes in CNE2-based models, at least in part through modulation of ITGB1-associated FAK\/AKT signaling.<\/jats:p>","DOI":"10.3390\/ijms27115045","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T06:17:31Z","timestamp":1780467451000},"page":"5045","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["rRGD3mu, a Triple-RGD Recombinant Peptide, Suppresses Malignant Phenotypes in Nasopharyngeal Carcinoma-Associated Models Through the Modulation of ITGB1-Associated FAK\/AKT Signaling"],"prefix":"10.3390","volume":"27","author":[{"given":"Qianhui","family":"Yuan","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Dalian Medical University, Dalian 116044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuxin","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Dalian Medical University, Dalian 116044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaotong","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Dalian Medical University, Dalian 116044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyu","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Liaoning Normal University, Dalian 116081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuebin","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Liaoning Normal University, Dalian 116081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jihong","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Dalian Medical University, Dalian 116044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei","family":"Lv","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology and Head and Neck Surgery, Dalian Medical University, Dalian 116100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jihong","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Liaoning Normal University, Dalian 116081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-6166-2783","authenticated-orcid":false,"given":"Li","family":"Lv","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Dalian Medical University, Dalian 116044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1056\/NEJMra1715715","article-title":"Head and neck cancer","volume":"382","author":"Chow","year":"2020","journal-title":"N. 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