Additive effects of oral fluoropyrimidine derivative S-1 and radiation on human hypopharyngeal cancer xenografts

Acta Otolaryngol. 2008 Aug;128(8):936-40. doi: 10.1080/00016480701784999.

Abstract

Conclusion: The results presented here provide evidence of the enhancing effect of oral fluoropyrimidine derivative S-1 in concomitant chemoradiotherapy for head and neck cancer and further insights into its biological mechanism.

Objective: To investigate the additive effect of S-1 and radiation for human hypopharyngeal cancer.

Materials and methods: Nude mice bearing hypopharyngeal cancer cells (H891) were used for an in vivo model. S-1 was administered at a volume of 0.01 mg/g body weight per mouse for 14 days, and tumors were irradiated with 2.0 Gy on days 1 and 8. Mice treated with either radiation or S-1 alone were used as controls. The growth of tumors in each group was measured and, after completion of the treatment, a focused DNA array was used to determine mRNA expression levels in the tumors of 132 genes related to 5-fluorouracil (5-FU), radiation or carcinogenesis.

Results: The additive antitumor effect of S-1 and radiation was statistically confirmed on day 14 (p=0.01). DNA array assay showed significant changes in expression of several genes, including DNA repair gene POLD, angiogenesis-related genes bFGF and TP, DNA topoisomerase TOP2A, and nucleoside transporter gene ENT1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Antimetabolites, Antineoplastic / administration & dosage*
  • Combined Modality Therapy
  • Drug Combinations
  • Fluorouracil / administration & dosage
  • Humans
  • Hypopharyngeal Neoplasms / drug therapy*
  • Hypopharyngeal Neoplasms / pathology
  • Hypopharyngeal Neoplasms / radiotherapy*
  • Male
  • Mice
  • Mice, Nude
  • Oxonic Acid / administration & dosage*
  • Tegafur / administration & dosage*
  • Tumor Burden
  • Xenograft Model Antitumor Assays

Substances

  • Antimetabolites, Antineoplastic
  • Drug Combinations
  • S 1 (combination)
  • Tegafur
  • Oxonic Acid
  • Fluorouracil