Please use this identifier to cite or link to this item: http://hdl.handle.net/20.500.11861/7388
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dc.contributor.authorZhu, Yingen_US
dc.contributor.authorKe, Kun-Binen_US
dc.contributor.authorXia, Zhong-Kunen_US
dc.contributor.authorLi, Hong-Jianen_US
dc.contributor.authorSu, Rongen_US
dc.contributor.authorDong, Chaoen_US
dc.contributor.authorZhou, Feng-Meien_US
dc.contributor.authorWang, Linen_US
dc.contributor.authorChen, Rongen_US
dc.contributor.authorWu, Shi-guoen_US
dc.contributor.authorZhao, Huien_US
dc.contributor.authorGu, Pengen_US
dc.contributor.authorProf. LEUNG Kwong Saken_US
dc.contributor.authorWong, Man-Honen_US
dc.contributor.authorLu, gangen_US
dc.contributor.authorZhang, Jian-yingen_US
dc.contributor.authorJiang, Bing- Huaen_US
dc.contributor.authorQiu, Jian-Geen_US
dc.contributor.authorShi, Xi-Nanen_US
dc.contributor.authorLin, Marie, Chia-mien_US
dc.date.accessioned2023-02-20T10:16:55Z-
dc.date.available2023-02-20T10:16:55Z-
dc.date.issued2021-
dc.identifier.citationMolecular Medicine 27, 2021, vol. 15en_US
dc.identifier.issn1528-3658-
dc.identifier.urihttp://hdl.handle.net/20.500.11861/7388-
dc.description.abstractBackground Cyclin-dependent kinases 2/4/6 (CDK2/4/6) play critical roles in cell cycle progression, and their deregulations are hallmarks of hepatocellular carcinoma (HCC). Methods We used the combination of computational and experimental approaches to discover a CDK2/4/6 triple-inhibitor from FDA approved small-molecule drugs for the treatment of HCC. Results We identified vanoxerine dihydrochloride as a new CDK2/4/6 inhibitor, and a strong cytotoxicdrugin human HCC QGY7703 and Huh7 cells (IC50: 3.79 μM for QGY7703and 4.04 μM for Huh7 cells). In QGY7703 and Huh7 cells, vanoxerine dihydrochloride treatment caused G1-arrest, induced apoptosis, and reduced the expressions of CDK2/4/6, cyclin D/E, retinoblastoma protein (Rb), as well as the phosphorylation of CDK2/4/6 and Rb. Drug combination study indicated that vanoxerine dihydrochloride and 5-Fu produced synergistic cytotoxicity in vitro in Huh7 cells. Finally, in vivo study in BALB/C nude mice subcutaneously xenografted with Huh7 cells, vanoxerine dihydrochloride (40 mg/kg, i.p.) injection for 21 days produced significant anti-tumor activity (p < 0.05), which was comparable to that achieved by 5-Fu (10 mg/kg, i.p.), with the combination treatment resulted in synergistic effect. Immunohistochemistry staining of the tumor tissues also revealed significantly reduced expressions of Rb and CDK2/4/6in vanoxerinedihydrochloride treatment group. Conclusions The present study isthe first report identifying a new CDK2/4/6 triple inhibitor vanoxerine dihydrochloride, and demonstrated that this drug represents a novel therapeutic strategy for HCC treatment.en_US
dc.language.isoenen_US
dc.relation.ispartofMolecular Medicineen_US
dc.titleDiscovery of vanoxerine dihydrochloride as a CDK2/4/6 triple-inhibitor for the treatment of human hepatocellular carcinomaen_US
dc.typePeer Reviewed Journal Articleen_US
dc.identifier.doi10.1186/s10020-021-00269-4-
item.fulltextNo Fulltext-
crisitem.author.deptDepartment of Applied Data Science-
Appears in Collections:Applied Data Science - Publication
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