Ectopic expression of LKB1 increases the expression of CDA. (A) CDA and RRM1 expression in wild-type and gemcitabine-resistant MDA-MB-231 cells was analyzed by western blot analysis. The two enzymes were upregulated in the gemcitabine-resistant subline. (B) Western blot analysis of CDA and RRM1 expression in cells. LKB1 increased CDA expression. (C) Metabolism and mechanism of gemcitabine in the cytoplasm. CDA is the enzyme that deaminizes gemcitabine to dFdU, eliminating the anticancer effect of gemcitabine. RRM1 is a subunit of RNR, which is the key enzyme involved in the production of the deoxyribonucleotide pool and DNA synthesis (12). LKB1, liver kinase B1; CDA, cytidine deaminase; RNR, ribonucleotide reductase; RRM1, ribonucleoside-diphosphate reductase; dFdCMP, difluoro-deoxyuridine monophosphate; dFdCDP, difluoro-deoxyuridine diphosphate; dFdCTP, difluoro-deoxyuridine triphosphate; WT, wild type.