Possible mechanisms of acquired resistance to 5-FU in human colon cancer

AIM: To explore the mechanisms of resistance to 5-fluorouracil(5-FU) in human colon cancer cells.METHODS: 5-FU-resistant cell lines were established and their IC50 were calculated by detection of cell survival rate.Western blotting was performed to analyze the expression of several proteins,by which the possible mechanisms of acquired resistance to 5-FU were determined in human colon cancer cells.RESULTS: The resistant cells were resistant to 5-FU-induced S phase arrest as well as the expression of DNA damage marker-phosphor-histone H2A.X.Furthermore,data demonstrated that over-expression of Bik,Bcl-Xs,and Bcl-XL proteins were observed in 5-FU-resistant cell lines.However,the DLD1/Bcl-XL cells were only partially resistant to 5-FU-induced apoptosis,but not 5-FU-induced S phase arrest and phosphor-histone H2A.X.CONCLUSION: Over-expression of Bcl-XL protein certainly contributes to acquired 5-FU resistance in human colon caners,but has no effect on 5-FU-induced DNA damage and cell cycle disorder,suggesting that other mechanisms are involved in acquired resistance to 5-FU in human colon cancer.