The c-MYC-ABCB5 axis plays a pivotal role in 5-fluorouracil resistance in human colon cancer cells.

摘要: c-MYC overexpression is frequently observed in various cancers including colon cancer and regulates many biological activities such as aberrant cell proliferation, apoptosis, genomic instability, immortalization drug resistance. However, the mechanism by which confers resistance remains to be fully elucidated. In this study, we found that expression level primary colorectal tissues correlated with recurrence rate following 5-fluorouracil (5-FU)-based adjuvant chemotherapy. Supporting finding, of exogenous increased survival 5-FU treatment human cells, knockdown endogenous decreased it. Furthermore, ABCB5, involved Using a chromatin immunoprecipitation assay, bound ABCB5 promoter region. inhibitor (10058-F4) inhibited binding promoter, leading decrease level. expected, was 5-FU-resistant cells. Finally, using xenograft murine model, combined 10058-F4 significantly tumorigenicity nude mice compared or alone. presence absence 5-FU. contrast, alone Taken together, these results suggest through regulating