RESUMEN
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.
RESUMEN
AIM:To study the effect of bcr - abl gene antisense phosphorothioate oligonucleotides(Aspo) on K562 cell line and explore its significance in chronic myelogencous leukemia (CML) gene therapy. METHODS: Cells were exposed to oligomers, observed by inverted microscope. Cells inhibitory rate were determined by 0.4% trypan blue exclusion. CFU - K562 were cultured in 0.8% methylcellulose. P210 was measured by flow cytometry. RESULTS:K562 cells were treated with Aspo, they still grew in clone state and show antisense sequence specific and dose dependent. When the concentration of Aspo was more than 5?mol/L, the growth of cells was inhibited and P210 was down regulated or completely suppressed, and the greatest growth inhibition was at 120h. There was significant inhibition of cell proliferation in a rang of cells number from 1 ? 10-4/mL to 5 ? 10-4/mL after treatment with 10?mol/L Aspo. b2a2 Aspo was also effect on K562 cells which expressing b3a2 mRNA. CONCLUSION: bcr - abl Aspo has a specific growth inhibition effect on K562 cells, and worths further study in CML gene therapy.