Please use this identifier to cite or link to this item:
http://hdl.handle.net/20.500.11861/7388
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Zhu, Ying | en_US |
dc.contributor.author | Ke, Kun-Bin | en_US |
dc.contributor.author | Xia, Zhong-Kun | en_US |
dc.contributor.author | Li, Hong-Jian | en_US |
dc.contributor.author | Su, Rong | en_US |
dc.contributor.author | Dong, Chao | en_US |
dc.contributor.author | Zhou, Feng-Mei | en_US |
dc.contributor.author | Wang, Lin | en_US |
dc.contributor.author | Chen, Rong | en_US |
dc.contributor.author | Wu, Shi-guo | en_US |
dc.contributor.author | Zhao, Hui | en_US |
dc.contributor.author | Gu, Peng | en_US |
dc.contributor.author | Prof. LEUNG Kwong Sak | en_US |
dc.contributor.author | Wong, Man-Hon | en_US |
dc.contributor.author | Lu, gang | en_US |
dc.contributor.author | Zhang, Jian-ying | en_US |
dc.contributor.author | Jiang, Bing- Hua | en_US |
dc.contributor.author | Qiu, Jian-Ge | en_US |
dc.contributor.author | Shi, Xi-Nan | en_US |
dc.contributor.author | Lin, Marie, Chia-mi | en_US |
dc.date.accessioned | 2023-02-20T10:16:55Z | - |
dc.date.available | 2023-02-20T10:16:55Z | - |
dc.date.issued | 2021 | - |
dc.identifier.citation | Molecular Medicine 27, 2021, vol. 15 | en_US |
dc.identifier.issn | 1528-3658 | - |
dc.identifier.uri | http://hdl.handle.net/20.500.11861/7388 | - |
dc.description.abstract | Background 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.iso | en | en_US |
dc.relation.ispartof | Molecular Medicine | en_US |
dc.title | Discovery of vanoxerine dihydrochloride as a CDK2/4/6 triple-inhibitor for the treatment of human hepatocellular carcinoma | en_US |
dc.type | Peer Reviewed Journal Article | en_US |
dc.identifier.doi | 10.1186/s10020-021-00269-4 | - |
item.fulltext | No Fulltext | - |
crisitem.author.dept | Department of Applied Data Science | - |
Appears in Collections: | Applied Data Science - Publication |
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