Cyclooxygenase-2 inhibitors enhance the antileukemia activity of STI571 / 中国病理生理杂志

ABSTRACT

AIM: To investigate whether celecoxib,a cyclooxygenase-2(COX-2) inhibitor,potentiates the anti-leukemia activity of STI571 in K562 cells.METHODS: K562 cells were treated with STI571,celecoxib or combination of both at different concentrations in suspension culture.Cell proliferation was documented by MTT assay,and cell apoptosis was determined by flow cytometry and morphology.Meanwhile,RT-PCR was applied to analyze the probable mechanism underlying the effects of the drugs.RESULTS: The combination of STI571 and celecoxib dramatically suppressed the proliferation of K562 cells,in which 0.25 ?mol/L STI571 and 40.0 ?mol/L celecoxib enhanced the inhibiting rate to 76.1%?1.6%.Furthermore,the combining administration of drugs significantly promoted the apoptosis induced by STI571,which showed characteristic changes of morphologic features and increase in sub-G_1 cells.By using RT-PCR technique,the expression of COX-2 had no decline by single administration of celecoxib or STI571.However,a progressive down-regulation was caused by coadministration of two drugs.In contrast with COX-2,the expression of VEGF had no changes at any time.CONCLUSION: The administration of celecoxib alone only inhibits the proliferation of K562 cells.Combination treatment with STI571 and celecoxib promotes the apoptosis induced by STI571.