Possible mechanisms of acquired resistance to 5-FU in human colon cancer / 中国病理生理杂志

ABSTRACT

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 IC50 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.