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

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

Research output: Contribution to journalArticle

12 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1148-1156
Number of pages9
JournalInternational journal of oncology
Volume41
Issue number3
DOIs
Publication statusPublished - 2012 Sep 1
Externally publishedYes

Keywords

  • 5-fluorouracil
  • 5-fluorouracil metabolic enzymes
  • Docetaxel
  • Oral squamous cell carcinoma
  • Sequential treatment

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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  • Cite this

    Tamatani, T., Ferdous, T., Takamaru, N., Hara, K., Kinouchi, M., Kuribayashi, N., Ohe, G., Uchida, D., Nagai, H., Fujisawa, K., & Miyamoto, Y. (2012). Antitumor efficacy of sequential treatment with docetaxel and 5-fluorouracil against human oral cancer cells. International journal of oncology, 41(3), 1148-1156. https://doi.org/10.3892/ijo.2012.1544