{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T03:24:29Z","timestamp":1792034669434,"version":"4.4.0"},"reference-count":42,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,4,6]],"date-time":"2025-04-06T00:00:00Z","timestamp":1743897600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82374210"],"award-info":[{"award-number":["82374210"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Phytotherapy Research"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Hepatoblastoma (HB), the most common primary malignant liver tumor in children, is characterized by high metastatic potential and poor prognosis. <jats:italic>Ganoderma lucidum<\/jats:italic> polysaccharide (GLP), the main bioactive compound of <jats:italic>Ganoderma lucidum<\/jats:italic>, has not been fully investigated for its therapeutic effects on HB. This study aimed to evaluate the anti\u2010tumor effects of GLP on HB cells and explore the underlying biological mechanisms. GLP was chemically characterized using ultraviolet\u2013visible spectroscopy, monosaccharide composition analysis, Fourier transform infrared (FTIR) spectroscopy, and scanning electron microscopy. The effects of GLP on the malignant phenotype of HB cells were assessed using CCK\u20108, EdU, Transwell assays, and other standard in\u00a0vitro techniques. Mechanistic investigations included proteomics, western blotting, chromatin immunoprecipitation (ChIP), and dual\u2010luciferase reporter assays. In\u00a0vivo anti\u2010HB effects of GLP were evaluated through animal models. Crude GLP, exhibiting anti\u2010tumor activity, was prepared through water extraction, alcohol precipitation, and column chromatography. In\u00a0vitro, GLP inhibited proliferation, invasion, and induced apoptosis in HuH6 and HepG2 cells. In\u00a0vivo, GLP suppressed tumor growth in a dose\u2010dependent manner. Mechanistically, GLP induced cellular senescence by downregulating histone deacetylase 4 (HDAC4) expression and enhancing p16 histone acetylation, which activated the p16\u2010retinoblastoma (p16\u2010RB) pathway and suppressed the malignant phenotype of HB cells. Furthermore, overexpression of HDAC4 reversed the senescence\u2010inducing effects of GLP. GLP inhibits HB progression by promoting cellular senescence via the HDAC4\u2010p16\u2010RB axis. These findings establish a mechanistic link between GLP's anti\u2010tumor activity and cellular senescence, providing new insights for its potential clinical application.<\/jats:p>","DOI":"10.1002\/ptr.8493","type":"journal-article","created":{"date-parts":[[2025,4,6]],"date-time":"2025-04-06T23:44:56Z","timestamp":1743983096000},"page":"2625-2640","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Inhibition of Hepatoblastoma by <i>Ganoderma Lucidum<\/i> Polysaccharide via the Induction of <scp>HDAC4<\/scp>\u2010p16\u2010<scp>RB<\/scp> Axis\u2010Mediated Cellular Senescence"],"prefix":"10.1002","volume":"39","author":[{"given":"Ting","family":"Ye","sequence":"first","affiliation":[{"name":"School of Integrated Chinese and Western Medicine Anhui University of Chinese Medicine  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Ge","sequence":"additional","affiliation":[{"name":"School of Integrated Chinese and Western Medicine Anhui University of Chinese Medicine  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Pharmacy Anhui University of Chinese Medicine  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hang","family":"Gao","sequence":"additional","affiliation":[{"name":"School of Integrated Chinese and Western Medicine Anhui University of Chinese Medicine  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng\u2010cheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Zhejiang Chinese Medical University  Hangzhou 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