The role of dihydropyrimidine dehydrogenase expression in resistance to 5-fluorouracil in head and neck squamous cell carcinoma cells

Ryuji Yasumatsu, Torahiko Nakashima, Hideoki Uryu, Muneyuki Masuda, Naoya Hirakawa, Hideki Shiratsuchi, Kichinobu Tomita, Masakazu Fukushima, Shizuo Komune

研究成果: Contribution to journalArticle査読

16 被引用数 (Scopus)

抄録

5-Fluorouracil (5-FU) is one of the most widely used chemotherapeutic drugs to treat cancer patients. However, the presence of drug resistant tumor cells may cause a poor response to 5-FU based chemotherapy. Dihydropyrimidine dehydrogenase (DPD) is the rate-limiting enzyme in the degradation of pyrimidine bases and is also responsible for the degradation of 5-FU. In this study, we examined whether DPD expression affects the cytotoxic activity of 5-FU against head and neck squamous cell carcinoma (HNSCC) and the role of DPD in the biological regulation of HNSCC. We constitutively expressed the DPD cDNA in a HNSCC cell line. The effect of DPD expression on in vitro cell growth, cell cycle and 5-FU cytotoxicity was examined. In addition, we also evaluated the association between DPD expression and the proliferation of tumor cells in surgical specimens, and prognosis of the patients with HNSCC. DPD overexpression decreases the cytotoxicity of 5-FU. CDHP, a strong DPD inhibitor, enhances the cytotoxic effect of 5-FU in HNSCC cells in vitro. DPD expression level does not effect cell proliferation and does not seem to have prognostic value in HNSCC. The present results strongly indicate that DPD expression plays an important role in the sensitivity of HNSCC to 5-FU chemotherapy, suggesting the possibility of personalized chemotherapy including the prediction of response and adverse effects.

本文言語英語
ページ(範囲)141-147
ページ数7
ジャーナルOral Oncology
45
2
DOI
出版ステータス出版済み - 2 2009

All Science Journal Classification (ASJC) codes

  • 口腔外科
  • 腫瘍学
  • 癌研究

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