Effect of Thymidine Phosphorylase Gene Demethylation on Sensitivity to 5-Fluorouracil in Colorectal Cancer Cells.
Anticancer Res
; 42(2): 837-844, 2022 Feb.
Article
in En
| MEDLINE
| ID: mdl-35093881
ABSTRACT
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 ANDMETHODS:
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.Key words
Full text:
1
Database:
MEDLINE
Main subject:
Thymidine Phosphorylase
/
Colorectal Neoplasms
/
Fluorouracil
/
Antimetabolites, Antineoplastic
Type of study:
Diagnostic_studies
Language:
En
Journal:
Anticancer Res
Year:
2022
Type:
Article