徳島大学 教育・研究者情報データベース(EDB)

1. 玉谷 哲也

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2. 髙丸 菜都美([徳島大学.病院.診療科.歯科口腔外科.口腔外科])

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3. (英) Hara Kanae / (日) 原 香苗 / (読) はら かなえ

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4. (英) Kinouchi Makoto / (日) 木内 誠 / (読) きのうち まこと

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5. 栗林 伸行

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6. 大江 剛

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7. 内田 大亮

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8. 藤澤 健司

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9. 永井 宏和

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10. 宮本 洋二

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(英) Bortezomib-enhanced radiosensitization through the suppression of radiation-induced nuclear factor B activity in human oral cancer cells.

(英) 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.

1. (英) Animals
2. (英) Antineoplastic Agents
3. (英) Apoptosis
4. (英) Boronic Acids
5. (英) Cell Line, Tumor
6. (英) Cell Proliferation
7. (英) Female
8. (英) Humans
9. (英) I-kappa B Proteins
10. (英) Interleukin-6
11. (英) Interleukin-8
12. (英) Mice
13. (英) Mice, Inbred BALB C
14. (英) Mice, Nude
15. (英) Mouth Neoplasms
16. (英) NF-kappa B
17. (英) Neoplasm Transplantation
18. (英) Neovascularization, Pathologic
19. (英) Poly(ADP-ribose) Polymerases
20. (英) Pyrazines
21. (英) Radiation-Sensitizing Agents
22. (英) Transcription Factor RelA
23. (英) Vascular Endothelial Growth Factor A
24. (英) Xenograft Model Antitumor Assays

1. (英) Article.ELocationID: 10.3892/ijo.2013.1786

2. (英) Article.PublicationTypeList.PublicationType: Journal Article

3. (英) Article.PublicationTypeList.PublicationType: Research Support, Non-U.S. Gov't