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ID 113602
Title Alternative
ANTI-TUMOR EFFICACY OF DOCETAXEL AND 5-FLUOROURACIL
Author
Tamatani, Tetsuya The University of Tokushima KAKEN Search Researchers
Ferdous, Tarannum The University of Tokushima
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
Nagai, Hirokazu The University of Tokushima KAKEN Search Researchers
Fujisawa, Kenji The University of Tokushima KAKEN Search Researchers
Keywords
oral squamous cell carcinoma
5-fluorouracil
docetaxel
sequential treatment
5-fluorouracil metabolic enzymes
Content Type
Journal Article
Description
Docetaxel (DOC) and 5-fluorouracil (5-FU) are important anticancer agents widely used in the treatment of a variety of cancers including oral squamous cell carcinoma (OSCC). The purpose of this study was to determine the antitumor efficacy of the sequential administration of DOC and 5-FU against OSCC cells (B88 and CAL27 cells) in vitro and in vivo. In in vitro growth inhibition assays, sequential treatment with DOC followed by 5-FU was more effective in inhibiting cancer cell growth than 5-FU followed by DOC, single treatment with DOC or 5-FU, or combined treatment with DOC and 5-FU. Furthermore, DOC followed by 5-FU significantly inhibited tumor growth in vivo compared to 5-FU followed by DOC. To understand the mechanisms underlying the enhanced growth inhibitory effect of the administration sequence, DOC followed by 5-FU, we examined the expression of 5-FU metabolic enzymes such as thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD) and orotate phosphoribosyl transferase (OPRT), which were known to regulate the antitumor effect of 5-FU, by real-time RT-PCR and western blot analysis. Downregulation of TS and DPD expression and upregulation of OPRT expression were induced by DOC treatment, suggesting that DOC enhanced the efficacy of 5-FU by altering the expression of its metabolic enzymes. These results indicate that sequential treatment with DOC followed by 5-FU could be a promising therapeutic strategy for oral cancer.
Journal Title
International Journal of Oncology
ISSN
10196439
17912423
NCID
AA10992511
Publisher
Spandidos Publications
Volume
41
Issue
3
Start Page
1148
End Page
1156
Published Date
2012-07-04
EDB ID
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
Publisher
departments
University Hospital
Oral Sciences