Antitumor efficacy of sequential treatment with docetaxel and 5-fluorouracil against human oral cancer cells

Tamatani,Tetsuya; Ferdous,Tarannum; Takamaru,Natsumi; Hara,Kanae; Kinouchi,Makoto; Kuribayashi,Nobuyuki; Ohe,Go; Uchida,Daisuke; Nagai,Hirokazu; Fujisawa,Kenji; Miyamoto,Youji

doi:10.3892/ijo.2012.1544

Antitumor efficacy of sequential treatment with docetaxel and 5-fluorouracil against human oral cancer cells

Authors:
- Tetsuya Tamatani
- Tarannum Ferdous
- Natsumi Takamaru
- Kanae Hara
- Makoto Kinouchi
- Nobuyuki Kuribayashi
- Go Ohe
- Daisuke Uchida
- Hirokazu Nagai
- Kenji Fujisawa
- Youji Miyamoto
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Affiliations: Department of Oral Surgery, Subdivision of Molecular Oral Medicine, Division of Integrated Sciences of Translational Research, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8504, Japan
Published online on: July 4, 2012 https://doi.org/10.3892/ijo.2012.1544
Pages: 1148-1156

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Abstract

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.

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