Abstract 3640: Increased anti-tumor effects of sequential docetaxel followed by 5-FU treatment against human oral cancer cells

Abstract

Abstract [Background] Docetaxel (TXT), a novel member of the taxoid family, and 5-fluorouracil (5-FU) are key drugs against oral cancer chemotherapy. The promising clinical activity of TXT and 5-FU has promoted considerable interest in combining these drugs. Although the combination treatment has been reported to improve the response rates, sequential treatment with TXT and 5-FU was unknown. [Purpose] The aim of this study was to evaluate the anti-tumor effects of sequential treatment with TXT and 5-FU against oral squamous cell carcinoma cells. [Methods and Results] Two human oral squamous cell carcinoma cell lines, B88 and CAL27 cells were used in this study. The effects of sequential treatment on the inhibition of tumor growth with TXT and 5-FU were investigated by 3-(4, 5-dimethylthiaol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometric analysis, and the xenograft on nude mice. In vivo study, B88 or CAL cells (5×106) were subcutaneously inoculated into the backs of nude mice. When the tumor reached 0.5 cm in diameter, tumor-bearing nude mice received either the intraperitoneal administration of TXT (10 mg/kg) alone, 5-FU (15 mg/kg) alone, TXT followed by 5-FU or 5-FU followed by TXT treatment. TXT followed by 5-FU treatment more effectively inhibited the tumor growth in vitro and in vivo, and induced apoptosis than 5-FU followed by TXT treatment. To elucidate the mechanisms underlying growth inhibitory effect of TXT followed by 5-FU, we examined the expression of 5-FU metabolic enzymes, thymidylate synthase (TS), dehydropyrimidine dehydrogenase (DPD), and ortate phosphorybosyl transferase (OPRT) by real-time PCR and western blot analysis. Down-regulation of TS and DPD expression, and up-regulation of OPRT expression were induced by TXT treatment compared with 5-FU, suggesting that they enhanced the efficacy of 5-FU. [Conclusions]These findings demonstrated that sequential treatment with TXT followed by 5-FU can be effective for the patients with oral squamous cell carcinoma. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3640.