ID | 113601 |
タイトル別表記 | BORTEZOMIB-ENHANCED RADIOSENSITIZATION IN HUMAN ORAL CANCER CELLS
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著者 |
Hara, Kanae
The University of Tokushima
Kinouchi, Makoto
The University of Tokushima
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キーワード | nuclear factor-κB
bortezomib
oral cancer
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資料タイプ |
学術雑誌論文
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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.
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掲載誌名 |
International Journal of Oncology
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ISSN | 10196439
17912423
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cat書誌ID | AA10992511
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出版者 | Spandidos Publications
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巻 | 42
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号 | 3
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開始ページ | 935
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終了ページ | 944
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発行日 | 2013-01-22
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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
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著者版フラグ |
出版社版
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部局 |
病院
歯学系
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