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