Annexin A1 is involved in resistance to 5-FU in colon cancer cells

Resistance to 5-fluorouracil (5-FU), a key drug in the treatment of colorectal cancer, is one of the major reasons for poor patient prognosis during cancer treatment. Annexin A1 (ANXA1) is a calcium-dependent phospholipid-linked protein that is associated with drug resistance, anti-inflammatory effects, regulation of cellular differentiation, proliferation and apoptosis. Although there have been several studies investigating ANXA1 expression in drug resistant cells, the role of ANXA1 is yet to be fully understood. We therefore, in this study, generated SW480 cells resistant to 5-FU (SW480/5-FU) to evaluate ANXA1 expression. When compared to the control cells, ANXA1 expression was significantly induced in the SW480/5-FU cells. We then revealed the role of ANXA1 expression in 5-FU resistance by using overexpression and knockdown methods in colon cancer cells. Overexpression of ANXA1 induced a significant increase of cell viability to 5-FU, whereas ANXA1 knockdown induced a significant decrease of cell viability to 5-FU. Further experiments revealed that ANXA1 expression was induced by hypoxia in colon cancer cells. These results suggest that ANXA1 expression may play a critical role in 5-FU resistance and may be induced by hypoxia during cancer progression. Our results provide a possible strategy to overcome 5-FU resistance by modulating ANXA1 expression.