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別タイトル
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
著者
青木 義朗
キーワード
ribonucleotide reductase
cisplatin
5-fluorouracil
γ-H2AX
RAD51
NDC
医学
抄録(英)
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.
作成年月日
2014-11-21
言語
英語
NII資源タイプ
学位論文
広大資料タイプ
学位論文
DCMIタイプ
text
フォーマット
application/pdf
著者版フラグ
ETD
権利情報
Copyright(c) by Author
関連情報(references)
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)
関連情報URL(references)
http://dx.doi.org/10.3892/ijo.2013.1899
学位記番号
甲第6190号
授与大学
広島大学(Hiroshima University)
学位名
博士(医学)
学位名の英名
Philosophy in Medical Science
学位の種類の英名
doctoral
学位授与年月日
2013-05-23
部局名
医歯薬学総合研究科