title: Antitumor efficacy of sequential treatment with docetaxel and 5-fluorouracil             against human oral cancer cells.
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.
authors: 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. ttama@dent.tokushima-u.ac.jp
authors: Tetsuya
authors: T
authors: Tamatani
authors: Tarannum
authors: T
authors: Ferdous
authors: Natsumi
authors: N
authors: Takamaru
authors: Kanae
authors: K
authors: Hara
authors: Makoto
authors: M
authors: Kinouchi
authors: Nobuyuki
authors: N
authors: Kuribayashi
authors: Go
authors: G
authors: Ohe
authors: Daisuke
authors: D
authors: Uchida
authors: Hirokazu
authors: H
authors: Nagai
authors: Kenji
authors: K
authors: Fujisawa
authors: Youji
authors: Y
authors: Miyamoto
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000096:biosynthesis; D000077143:Docetaxel; D015536:Down-Regulation; D005472:Fluorouracil / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009062:Mouth Neoplasms / Q000188:drug therapy*; D009962:Orotate Phosphoribosyltransferase / Q000096:biosynthesis; D043823:Taxoids / Q000494:pharmacology* / Q000627:therapeutic use; D013940:Thymidylate Synthase / Q000096:biosynthesis; D015854:Up-Regulation; D023041:Xenograft Model Antitumor Assays
chemical_list: D043823:Taxoids; D000077143:Docetaxel; D042943:Dihydrouracil Dehydrogenase (NADP); D013940:Thymidylate Synthase; D009962:Orotate Phosphoribosyltransferase; D005472:Fluorouracil