PT  - JOURNAL ARTICLE
AU  - MUNEYUKI KOYAMA
AU  - ERIKA OSADA
AU  - NUBUTAKE AKIYAMA
AU  - KEN ETO
AU  - YOSHINOBU MANOME
TI  - Effect of Thymidine Phosphorylase Gene Demethylation on Sensitivity to 5-Fluorouracil in Colorectal Cancer Cells
AID  - 10.21873/anticanres.15541
DP  - 2022 Feb 01
TA  - Anticancer Research
PG  - 837--844
VI  - 42
IP  - 2
4099  - http://ar.iiarjournals.org/content/42/2/837.short
4100  - http://ar.iiarjournals.org/content/42/2/837.full
SO  - Anticancer Res2022 Feb 01; 42
AB  - 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.