Furthermore, high rates of OXPHOS represent another crucial mechanism contributing to 5-FU resistance.43 Notably, in patients with 5-FU-exposed CRC resected liver metastases, there was a SIRT1/PGC1α-dependent increase in OXPHOS.44 Consistent with these observations, combined treatment with 5-FU and antimycin A, an inhibitor of mitochondrial complex III, has been shown to promote cell death in resistant CRC.45 Our study provided molecular insights into how NT219 sensitizes CRC BM to 5-FU by inhibiting β-catenin. Here, SIRT1 is linked to colorectal carcinoma.