著作: [玉谷 哲也]/Ferdous Tarannum/[髙丸 菜都美]/原 香苗/木内 誠/[栗林 伸行]/[大江 剛]/[内田 大亮]/[永井 宏和]/[藤澤 健司]/[宮本 洋二]/Antitumor efficacy of sequential treatment with docetaxel and 5-fluorouracil against human oral cancer cells/[International Journal of Oncology]
(英) Antitumor efficacy of sequential treatment with docetaxel and 5-fluorouracil against human oral cancer cells
(英) 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.
International Journal of Oncology(International Center for Cancer Research)
|年月日||必須||2012年 9月 初日|