並列タイトル等5-Aza-2-deoxycytidine enhances thesensitivity of 5-fluorouracil by demethylation of the thymidine phosphorylase promoter
学位博士(医学)
Doctor of Philosophy in Medical Science
一般注記博士論文全文, 博士論文要旨, 最終試験結果の要旨, 論文審査の要旨
Background/Aim: 5-Aza-2-deoxycytidine (5-Aza-CdR) enhances the sensitivity to 5-fluorouracil (5-FU), but the molecular mechanism is not fully understood. The aim of this study was to investigate the molecular mechanism that enhances the sensitivity to 5-FU treated with 5-Aza-CdR via thymidine phosphorylase (TP). Materials and Methods: The sensitivity to drugs was determined on several cancer cell lines by the MTT assay. Protein and mRNA levels were examined by immunoblot and RT-PCR, respectively. Gene silencing, binding of Sp1 to DNA and methylation of DNA was performed by siRNA, ChIP assay and sodium bisulfate genomic sequencing, respectively. Results: Sp1-binding sites in the TP promoter were methylated in epidermoid carcinoma. 5-Aza-CdR demethylated Sp1-binding sites and enhanced sensitivity to 5-FU. Conclusion: Demethylation of Sp1-binding sites by 5-Aza-CdR was a key factor enhancing 5-FU sensitivity, which may enable more effective treatments for cancer patients with the combination of 5-Aza-CdR and 5-FU.YUKIHIKO NISHIZAWA, RYUJI IKEDA, MASATATSU YAMAMOTO, KOHICHI KAWAHARA, YOSHINARI SHINSATO, KENTARO MINAMI, MINA NITTA, HIDEYUKI TERAZONO, SHIN-ICHI AKIYAMA, TATSUHIKO FURUKAWA and YASUO TAKEDA5-Aza-2-deoxycytidine Enhances the Sensitivity of 5-Fluorouracil by Demethylation of the Thymidine Phosphorylase PromoterAnticancer Research, 2019, 39(8) p.4129-4136DOI: https://doi.org/10.21873/anticanres.13571
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