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ID 113601
タイトル別表記
BORTEZOMIB-ENHANCED RADIOSENSITIZATION IN HUMAN ORAL CANCER CELLS
著者
玉谷, 哲也 The University of Tokushima KAKEN研究者をさがす
Hara, Kanae The University of Tokushima
Kinouchi, Makoto The University of Tokushima
栗林, 伸行 The University of Tokushima KAKEN研究者をさがす
大江, 剛 The University of Tokushima KAKEN研究者をさがす
内田, 大亮 The University of Tokushima KAKEN研究者をさがす
藤澤, 健司 The University of Tokushima KAKEN研究者をさがす
永井, 宏和 The University of Tokushima KAKEN研究者をさがす
キーワード
nuclear factor-κB
bortezomib
oral cancer
資料タイプ
学術雑誌論文
抄録
Oral cancer cells have a significantly augmented nuclear factor-κB (NF-κB) activity and the inhibition of this activity suppresses tumor growth. Bortezomib is a proteasome inhibitor and a drug used for molecular-targeted therapy (targets NF-κB). In this study, we investigated whether bortezomib would be effective as an inhibitor of proliferation and a radiosensitizer for the treatment of oral cancer. We demonstrate that bortezomib inhibits NF-κB activity and cell proliferation. The combined treatment with bortezomib and radiation (RT) suppressed NF-κB activity and cell growth in vitro and in vivo compared with RT treatment alone. To investigate the mechanisms by which bortezomib suppresses tumor growth, the expression of signaling molecules downstream of NF-κB were examined by ELISA. The combined treatment significantly inhibited the radiation‑induced production of angiogenic factors and decreased the number of blood vessels in the tumor tissues. Although the expression of anti‑apoptotic proteins was upregulated by RT, bortezomib downregulated the RT-induced expression of these proteins. Moreover, the expression of cleaved poly(ADP‑ribose) polymerase in vitro and in vivo was enhanced by bortezomib, indicating that bortezomib inhibits tumor growth by inducing apoptosis. This study clearly demonstrates that bortezomib significantly inhibits tumor growth and that the combined treatment with bortezomib and RT results in a significant inhibition of tumor growth. The mechanisms underlying the inhibition of tumor growth by bortezomib include the suppression of angiogenesis and the induction of apoptosis. A novel molecular targeting therapy including bortezomib may be effective in the treatment of oral cancer by suppressing NF-κB activity.
掲載誌名
International Journal of Oncology
ISSN
10196439
17912423
cat書誌ID
AA10992511
出版者
Spandidos Publications
42
3
開始ページ
935
終了ページ
944
発行日
2013-01-22
EDB ID
出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
出版社版
部局
病院
歯学系