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: Tetsuya Tamatani, Tarannum Ferdous, Natsumi Takamaru, Kanae Hara, Makoto Kinouchi, Nobuyuki Kuribayashi, Go Ohe, Daisuke Uchida, Hirokazu Nagai, Kenji Fujisawa, Youji Miyamoto
• Journal: International journal of oncology (Int J Oncol) Vol. 41 Issue 3 Pg. 1148-56 (Sep 2012) ISSN: 1791-2423 [Electronic] Greece
• PMID: 22766915 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Taxoids
• Docetaxel
• Dihydrouracil Dehydrogenase (NADP)
• Thymidylate Synthase
• Orotate Phosphoribosyltransferase
• Fluorouracil

Topics

• Animals
• Antineoplastic Combined Chemotherapy Protocols (pharmacology, therapeutic use)
• Cell Line, Tumor
• Dihydrouracil Dehydrogenase (NADP) (biosynthesis)
• Docetaxel
• Down-Regulation
• Fluorouracil (metabolism, pharmacology, therapeutic use)
• Humans
• Mice
• Mice, Nude
• Mouth Neoplasms (drug therapy)
• Orotate Phosphoribosyltransferase (biosynthesis)
• Taxoids (pharmacology, therapeutic use)
• Thymidylate Synthase (biosynthesis)
• Up-Regulation
• Xenograft Model Antitumor Assays