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

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

来源：International Journal of Oncology, 2012, 41(3): 1148-1156.

DOI：10.3892/ijo.2012.1544

• oral squamous cell carcinoma
• 5-fluorouracil
• docetaxel
• sequential treatment
• 5-fluorouracil metabolic enzymes

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.

• 出版日期2012-9