Histone/protein deacetylase SIRT1 is an anticancer therapeutic target

[摘要] SIRT1, a member of the NAD⁺-dependent histone/protein deacetylase family, is involved in chromatin remodeling, DNA repair, and stress response and is a potential drug target. 5-fluorouracil (FU) and the S_N1-type DNA methylating agent temozolomide (TMZ) are anticancer agents. In this study, we demonstrate that sirt1 knockout mouse embryonic fibroblast cells are more sensitive to FU and DNA methylating agents than normal cells. Based on these findings, the chemotherapy efficacy of SIRT1 inhibitors in combination with FU or TMZ were tested with human breast cancer cells. We found that treatments combining SIRT1 inhibitors with FU or TMZ show synergistic reduction of cell viability and colony formation of breast cancer cells. Thus, inhibition of SIRT1 activity provides a novel anticancer strategy.

[学科分类] 肿瘤学

[关键词] Breast cancer;drug resistance;SIRT1 histone deacetylase;5-fluorouracil;methylating agents