{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T18:36:13Z","timestamp":1777055773292,"version":"3.51.4"},"reference-count":49,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T00:00:00Z","timestamp":1776988800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004608","name":"Natural Science Foundation of Jiangsu Province","doi-asserted-by":"publisher","award":["BK20251768"],"award-info":[{"award-number":["BK20251768"]}],"id":[{"id":"10.13039\/501100004608","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Construction Project of High Level Hospital of Jiangsu Province","award":["LCZX202506"],"award-info":[{"award-number":["LCZX202506"]}]}],"content-domain":{"domain":["www.plosgenetics.org"],"crossmark-restriction":false},"short-container-title":["PLoS Genet"],"abstract":"<jats:p>\n                    Emerging evidence reveals the pivotal involvement of mitochondrial metabolic dysregulation in glioblastoma (GBM) pathogenesis, considering mitochondrial metabolism as a potential therapeutic target. Nebivolol, a third-generation \u03b2-adrenergic receptor antagonist clinically employed in cardiovascular diseases, has recently exhibited notable anti-neoplastic properties. Nevertheless, its therapeutic efficacy and mechanistic underpinnings in GBM remain largely unexplored. In this investigation, we comprehensively assessed the impact of nebivolol on GBM cellular proliferation and elucidated its molecular mechanisms. Our findings revealed that nebivolol markedly suppressed the proliferation and clonogenic abilities of multiple GBM cell lines, concomitant with cell cycle arrest and apoptotic induction. Mechanistically, nebivolol impaired mitochondrial respiratory chain complex I activity, diminished adenosine triphosphate (ATP) synthesis, and augmented ROS production, collectively precipitating neoplastic cell apoptosis. Furthermore, nebivolol attenuated AKT\/mTOR\/4EBP1 signaling cascade activation, thereby impeding GBM malignant proliferation.\n                    <jats:italic>In vivo<\/jats:italic>\n                    studies corroborated these observations, demonstrating that nebivolol administration significantly attenuated orthotopic GBM xenograft progression and extended survival in tumor-bearing murine models. This study delineates a novel dual mechanism whereby nebivolol exerts anti-GBM effects through concurrent modulation of mitochondrial bioenergetics and AKT\/mTOR\/4EBP1 signaling transduction. These results provide robust preclinical evidence supporting nebivolol\u2019s clinical repurposing for GBM therapy.\n                  <\/jats:p>","DOI":"10.1371\/journal.pgen.1012120","type":"journal-article","created":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T17:41:07Z","timestamp":1777052467000},"page":"e1012120","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgen.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Nebivolol suppresses glioblastoma progression via dual modulation of mitochondrial metabolism and AKT\/mTOR\/4EBP1 signaling 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