CF10/LV overcomes acquired resistance to 5-FU/LV in colorectal cancer cells through downregulation of the c-Myc/ABCB5 axis.

ABSTRACT: Aim: Acquired resistance to 5-fluorouracil/leucovorin (5-FU/LV) frequently develops during treatment of metastatic colorectal (mCRC), but the causes are incompletely understood. We aim to: (i) identify the causes of 5-FU/LV resistance under physiological folate; and (ii) determine if a polymeric fluoropyrimidine (FP) CF10 remains potent to CRC cells selected for 5-FU/LV resistance. Methods: 5-FU/LV-resistant CRC cells were selected by repeated passaging with increasing 5-FU/LV concentrations, and resistance factors were calculated from dose-response studies. Basal and treatment-induced thymidylate synthase (TS), Myc, and ABCB5 were determined by RT-qPCR and Western blot. TS activity was determined using an in situ ³H-release assay. DNA topoisomerase 1 cleava

SUBMITTER: Okechukwu CC 

PROVIDER: S-EPMC12367397 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature