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ID 113601
Title Alternative
BORTEZOMIB-ENHANCED RADIOSENSITIZATION IN HUMAN ORAL CANCER CELLS
Author
Tamatani, Tetsuya The University of Tokushima KAKEN Search Researchers
Hara, Kanae The University of Tokushima
Kinouchi, Makoto The University of Tokushima
Ohe, Go The University of Tokushima KAKEN Search Researchers
Uchida, Daisuke The University of Tokushima KAKEN Search Researchers
Fujisawa, Kenji The University of Tokushima KAKEN Search Researchers
Nagai, Hirokazu The University of Tokushima KAKEN Search Researchers
Keywords
nuclear factor-κB
bortezomib
oral cancer
Content Type
Journal Article
Description
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.
Journal Title
International Journal of Oncology
ISSN
10196439
17912423
NCID
AA10992511
Publisher
Spandidos Publications
Volume
42
Issue
3
Start Page
935
End Page
944
Published Date
2013-01-22
EDB ID
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
Publisher
departments
University Hospital
Oral Sciences