例如:"lncRNA", "apoptosis", "WRKY"

5-Aza-2-deoxycytidine Enhances the Sensitivity of 5-Fluorouracil by Demethylation of the Thymidine Phosphorylase Promoter.

Anticancer Res.2019 Aug;39(8):4129-4136
Yukihiko Nishizawa 1 , Ryuji Ikeda 2 , Masatatsu Yamamoto 3 , Kohichi Kawahara 3 , Yoshinari Shinsato 3 , Kentaro Minami 3 , Mina Nitta 1 , Hideyuki Terazono 1 , Shin-Ichi Akiyama 3 , Tatsuhiko Furukawa 4 , Yasuo Takeda 5
Yukihiko Nishizawa 1 , Ryuji Ikeda 2 , Masatatsu Yamamoto 3 , Kohichi Kawahara 3 , Yoshinari Shinsato 3 , Kentaro Minami 3 , Mina Nitta 1 , Hideyuki Terazono 1 , Shin-Ichi Akiyama 3 , Tatsuhiko Furukawa 4 , Yasuo Takeda 5
+ et al

[No authors listed]

Author information
  • 1 Department of Clinical Pharmacy and Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
  • 2 Department of Pharmacy, University of Miyazaki Hospital, Miyazaki, Japan.
  • 3 Department of Molecular Oncology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
  • 4 Center for the Research of Advanced Diagnosis and Therapy of Cancer, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
  • 5 Department of Clinical Pharmacy and Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan takeda@m.kufm.kagoshima-u.ac.jp.

摘要


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.

KEYWORDS: 5-aza-2-deoxycytidine, 5-fluorouracil, methylation, thymidine phosphorylase