https://scholars.lib.ntu.edu.tw/handle/123456789/580246
標題: | CIP2A-mediated Akt activation plays a role in bortezomib-induced apoptosis in head and neck squamous cell carcinoma cells | 作者: | Lin Y.-C. Chen K.-C. CHING-CHOW CHEN ANN-LII CHENG Chen K.-F. |
公開日期: | 2012 | 卷: | 48 | 期: | 7 | 起(迄)頁: | 585-593 | 來源出版物: | Oral Oncology | 摘要: | Head and neck squamous cell carcinoma (HNSCC) is a worldwide disease with aggressive course and dismal outcome. Bortezomib, a proteasome inhibitor, has been approved clinically for hematological malignancies and demonstrated to have activities against solid tumors in vitro through inhibition of NF-kB activity. Here, we disclose that bortezomib induced apoptosis of HNSCC cells in vitro and in vivo through inhibition of cancerous inhibitor of protein phosphatase 2A (CIP2A)-mediated PP2A dependent Akt activation. HNSCC cells, including Ca9-22, SAS, and SCC-25, were treated with bortezomib and evaluated for viability, apoptosis, and signal transduction. Three HNSCC cells, including Ca9-22, SAS, and SCC-25, were sensitive to bortezomib with marked growth inhibition and apoptosis. We found phospho-Akt (p-Akt, Ser473) played a significant role in bortezomib-induced apoptosis. The activity of PP2A was significantly increased after the treatment of bortezomib without alternation of PP2A level or the dynamic interaction of PP2A-Akt. Silencing PP2A by small interference RNA (siRNA) abolished bortezomib-induced Akt inhibition and apoptosis. In addition, bortezomib inhibited CIP2A in pre-translational level in a dose- and time-dependent manner. Over-expression of CIP2A up-regulated p-Akt and protected HNSCC cells from bortezomib-induced apoptosis. Furthermore, xenograft model showed that bortezomib down-regulated CIP2A and p-Akt in SAS tumor cells. CIP2A is demonstrated to be a new therapeutic target of bortezomib in HNSCC. ? 2012 Elsevier Ltd. All rights reserved. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84862790962&doi=10.1016%2fj.oraloncology.2012.01.012&partnerID=40&md5=c4a46e95f5e7437f7e07c708e3075bdd https://scholars.lib.ntu.edu.tw/handle/123456789/580246 |
DOI: | 10.1016/j.oraloncology.2012.01.012 | SDG/關鍵字: | bortezomib; cancerous inhibitor of protein phosphatase 2A; phosphoprotein phosphatase 2A; protein kinase B; serine; small interfering RNA; unclassified drug; animal experiment; animal model; apoptosis; article; cancer cell; cancer inhibition; cell viability; drug mechanism; enzyme activation; enzyme activity; enzyme inhibition; enzyme phosphorylation; head and neck cancer; head and neck squamous cell carcinoma; in vitro study; in vivo study; male; mouse; nonhuman; priority journal; protein expression; signal transduction; squamous cell carcinoma; Animals; Antineoplastic Agents; Apoptosis; Autoantigens; Blotting, Western; Boronic Acids; Carcinoma, Squamous Cell; Cell Line, Tumor; Head and Neck Neoplasms; Male; Membrane Proteins; Mice; Mice, Nude; Neoplasms, Experimental; Polymerase Chain Reaction; Protein Phosphatase 2; Proto-Oncogene Proteins c-akt; Pyrazines; RNA, Small Interfering; Signal Transduction |
顯示於: | 醫學系 |
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