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Effect of Thymidine Phosphorylase Gene Demethylation on Sensitivity to 5-Fluorouracil in Colorectal Cancer Cells.
Koyama, Muneyuki; Osada, Erika; Akiyama, Nubutake; Eto, Ken; Manome, Yoshinobu.
Afiliación
  • Koyama M; Core Research Facilities, The Jikei University School of Medicine, Tokyo, Japan; takahadoctor@yahoo.co.jp.
  • Osada E; Department of Gastrointestinal Surgery, The Jikei University School of Medicine, Tokyo, Japan.
  • Akiyama N; Core Research Facilities, The Jikei University School of Medicine, Tokyo, Japan.
  • Eto K; Core Research Facilities, The Jikei University School of Medicine, Tokyo, Japan.
  • Manome Y; Department of Gastrointestinal Surgery, The Jikei University School of Medicine, Tokyo, Japan.
Anticancer Res ; 42(2): 837-844, 2022 Feb.
Article en En | MEDLINE | ID: mdl-35093881
BACKGROUND/AIM: Chemotherapy is used for recurrent and metastatic colorectal cancer, but the response rate of 5-fluorouracil (5-FU), the standard treatment for colorectal cancer, is low. We hypothesized that thymidine phosphorylase (TYMP) expression, a rate-limiting activating enzyme of 5-FU, is regulated by methylation of the gene promoter region, and demethylation of TYMP would increase sensitivity to 5-FU. MATERIALS AND METHODS: HCT116 colon cancer cells were treated with 5-aza-2'-deoxycytidine, a demethylating agent, and changes in TYMP transcription and sensitivity to 5-FU were evaluated. RESULTS: TYMP expression increased over 54-fold in HCT116 transfected with TYMP. The cytotoxicity of 5-FU increased up to 5.5-fold. In comparison, in HCT116 treated with 5-aza-2'-deoxycytidine, TYMP expression increased 5.8-fold. However, the cytotoxicity of 5-FU remained unchanged. CONCLUSION: Demethylating agent alone did not promote the cytotoxicity of 5-FU against colorectal cancer. To further increase the sensitivity to 5-FU, combination with adjuvant therapy focusing on metabolic pathways other than the TYMP pathway appear necessary.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Timidina Fosforilasa / Neoplasias Colorrectales / Fluorouracilo / Antimetabolitos Antineoplásicos Tipo de estudio: Diagnostic_studies Idioma: En Revista: Anticancer Res Año: 2022 Tipo del documento: Article

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Timidina Fosforilasa / Neoplasias Colorrectales / Fluorouracilo / Antimetabolitos Antineoplásicos Tipo de estudio: Diagnostic_studies Idioma: En Revista: Anticancer Res Año: 2022 Tipo del documento: Article