Effect of Thymidine Phosphorylase Gene Demethylation on Sensitivity to 5-Fluorouracil in Colorectal Cancer Cells.
Anticancer Res
; 42(2): 837-844, 2022 Feb.
Article
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| 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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Bases de datos:
MEDLINE
Asunto principal:
Timidina Fosforilasa
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Neoplasias Colorrectales
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Fluorouracilo
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Antimetabolitos Antineoplásicos
Tipo de estudio:
Diagnostic_studies
Idioma:
En
Revista:
Anticancer Res
Año:
2022
Tipo del documento:
Article