{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T07:37:38Z","timestamp":1790753858372,"version":"4.1.0"},"reference-count":41,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,12,22]],"date-time":"2023-12-22T00:00:00Z","timestamp":1703203200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Drug Development Research"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Everolimus, a known inhibitor of the mammalian target of rapamycin (mTOR), has shown uncertain efficacy in treating hepatoblastoma. This study delves into the potential anti\u2010hepatoblastoma properties of everolimus and its intricate relationship with autophagy and ferroptosis, both in vitro and in vivo. In vivo, tumor tissue from hepatoblastoma patient and human hepatoblastoma cell line HuH\u20106 were xenografted into nude mice to establish xenograft models for observing the effect of everolimus on tumor growth. In vitro, HuH\u20106 cells were cultured to evaluate the anti\u2010hepatoblastoma activity of everolimus. Transmission electron microscopy and microtubule\u2010associated proteins 1 light chain 3 (LC3), beclin 1, and p62 protein expressions were employed to investigate autophagy. Additionally, indicators of cell apoptosis, reactive oxygen species (ROS) and proteins associated with ferroptosis were measured to evaluate ferroptosis. The results demonstrate that everolimus treatment effectively induced the formation of autophagosomes in hepatoblastoma cells, upregulated the LC3II\/I ratio and beclin 1 expression, and downregulated p62 expression, indicating an enhanced autophagy level both in vitro and in vivo. Furthermore, everolimus treatment induced cell apoptosis, increased ROS level, elevated concentrations of malondialdehyde, 4\u2010hydroxynonenal, and iron content, while reducing the ratio of glutathione\/oxidized glutathione, and downregulating the protein expression of glutathione peroxidase 4 and solute carrier family 7 member 11, suggesting its ability to induce ferroptosis in hepatoblastoma cells. Importantly, the induction of ferroptosis by everolimus was significantly reversed in the presence of autophinib, an autophagy inhibitor, indicating the autophagy\u2010dependent of everolimus\u2010induced ferroptosis. Taken together, these findings suggest that everolimus holds promise as an effective anti\u2010hepatoblastoma drug, with its mechanism of action potentially involving the induction of autophagy\u2010dependent ferroptosis in hepatoblastoma cells.<\/jats:p>","DOI":"10.1002\/ddr.22140","type":"journal-article","created":{"date-parts":[[2023,12,22]],"date-time":"2023-12-22T08:19:20Z","timestamp":1703233160000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Everolimus inhibits hepatoblastoma by inducing autophagy\u2010dependent ferroptosis"],"prefix":"10.1002","volume":"85","author":[{"given":"Haijin","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Pediatric Surgery First Affiliated Hospital of Gannan Medical University Ganzhou Jiangxi China"},{"name":"Jiangxi Provincial Clinical Research Center for Vascular Anomalies The First Affiliated Hospital of GanNan Medical University Ganzhou Jiangxi 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