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Anti-Tumor Effect of the Mammalian Target of Rapamycin Inhibitor Everolimus in Oral Squamous Cell Carcinoma


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タイトル: Anti-Tumor Effect of the Mammalian Target of Rapamycin Inhibitor Everolimus in Oral Squamous Cell Carcinoma
著者: Naruse, Tomofumi / Yanamoto, Souichi / Yamada, Shin-ichi / Rokutanda, Satoshi / Kawakita, Akiko / Kawasaki, Goro / Umeda, Masahiro
発行日: 2015年 7月
出版者: Springer Netherlands
引用: Pathology & Oncology Research, 21(3), pp.765-773; 2015
抄録: The mammalian target of rapamycin (mTOR) has recently emerged as a promising target for therapeutic anti-cancer interventions in several human tumors. In present study, we investigated the expression of mTOR, and subsequently examined its relationship with clinicopathological factors and the anti-tumor effect of everolimus (also known as RAD001) in oral squamous cell carcinoma (OSCC). The expression of phosphorylated mTOR (p-mTOR) was immunohistochemically evaluated in specimens obtained from 70 OSCC patients who underwent radical surgery. The relationships between the expression of p-mTOR and clinicopathological factors and survival were determined. We also investigated the effect of everolimus on the OSCC cell lines, SAS, HSC-2, HSC-3, HSC-4, OSC-20, SCC25 and Ca9-22 by the MTT assay. We further evaluated whether mTOR contributed to cell functions by blocking its activity with everolimus, and confirmed the direct target by the Matrigel invasion assay, wound healing assay and Western blotting. p-mTOR was overexpressed in 37 tumors (52.8 %), and correlated with the T classification, N classification, and survival rate (P < 0.05). The treatment with everolimus significantly inhibited cell growth, and significantly reduced the expression of p-mTOR, downstream signaling proteins, and hypoxic related proteins as well as invasion and migration potentials (P < 0.05). The results of the present study suggest that everolimus may represent an attractive approach for the future treatment of OSCC.
キーワード: Everolimus / Hypoxia / mTOR / Oral cancer
URI: http://hdl.handle.net/10069/35836
ISSN: 12194956
DOI: 10.1007/s12253-014-9888-1
権利: © Arányi Lajos Foundation 2015 / The original publication is available at www.springerlink.com
資料タイプ: Journal Article
原稿種類: author
出現コレクション:130 学術雑誌論文

引用URI : http://hdl.handle.net/10069/35836

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