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

食道癌細胞株における5-フルオロウラシルにより誘導されるDNA障害へのリボヌクレオチドリダクターゼM1の関与

Aoki Yoshiro

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 forma-tion, 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 forma-tion 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.

ribonucleotide reductase

cisplatin

5-fluorouracil

γ-H2AX

RAD51

Medical sciences [ 490 ]

eng

Copyright(c) by Author

[Created] 2014-11-21

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 and SATOSHI TASHIRO; Involvement of ribonucleotide reductase-M1 in 5-fluorouracil-induced DNA damage in esophageal cancer cell lines; INTERNATIONAL JOURNAL OF ONCOLOGY 42: 1951-1960, 2013 (DOI: 10.3892/ijo.2013.1899) references

[DOI] http://dx.doi.org/10.3892/ijo.2013.1899 references

広島大学