Involvement of ribonucleotide reductase-M1 in 5-fluorouracil.-induced DNA damage in esophageal cancer cell lines

Yoshiro Aoki, Kenji Sakogawa, Jun Hihara, Manabu Emi, Yoichi Hamai, Kazuteru Kono, Lin Shi, Jiying Sun, Hiroyuki Kitao, Tsuyoshi Ikura, Hiroyuki Niida, Makoto Nakanishi, Morihito Okada, Satoshi Tashiro

研究成果: Contribution to journalArticle査読

7 被引用数 (Scopus)

抄録

5-Fluorouracil (5-FU) is one of the most well established chemotherapeutic agents in the treatment of esophageal cancer. Ribonucleotide reductase M1 (RRM-1) is the rate-limiting enzyme in de. novo DNA synthesis, and has been considered to play an important role in the 5-FU metabolic pathway. However, the means by which RRM-1 participates in the anticancer effects of 5-FU and cisplatin (CDDP) have not been well studied. Here, we show that RRM-1 significantly contributes to the induction of DNA damage by 5-FU in esophageal cancer cell lines. An assay of γ-H2AX focus formation, a marker of DNA damage, after 5-FU treatment revealed good correlation with the levels of RRM-1 protein expression. Moreover, the increased sensitivity and RAD51 focus formation induced by the combination treatment of 5-FU and CDDP were significantly repressed by RRM-1 depletion. These results suggest that RRM-1 is involved not only in the induction of DNA damage by 5-FU but also in the synergistic cytotoxic effect in the combination therapy of 5-FU and CDDP.

本文言語英語
ページ(範囲)1951-1960
ページ数10
ジャーナルInternational journal of oncology
42
6
DOI
出版ステータス出版済み - 6 2013

All Science Journal Classification (ASJC) codes

  • 腫瘍学
  • 癌研究

フィンガープリント

「Involvement of ribonucleotide reductase-M1 in 5-fluorouracil.-induced DNA damage in esophageal cancer cell lines」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル