Effects Of STI571 In Combination With As₂O₃ On Proliferation And Apoptosis Of The K562 Cells And Bcr-Abl, JAK-STAT Protein Level

Objective To investigate the effects of STI571 alone and in combination with AS₂O₃ on proliferation and apoptosis of the K562 cells; To observe the effects of STI571 alone and in combination with AS₂O₃ on Bcr-Abl, JAK2 and STAT5 protein tyrosine phosphorylation in K562 cells and to explore their molecular mechanism of antileukemia, to provide theoretical basis of the combination of the two drugs for clinical therapy of CML cases.Methods Cell proliferation was analyzed by the growth of cell and the viability of cell; Apoptosis was analyzed by cell morphology, Annexin-V/PI staining, DNA-PI staining, and DNA gel electrophoresis; Bcr-Abl, JAK2 and STAT5 protein tyrosine phosphorylation was studied by means of immunoprecipition and Western blot.Results After exposure to STI571 and/or As₂O₃, the growth of K562 cells was obviously inhibited and the viability of K562 cells was decreased; Typical apoptotic cell morphology was find by the Wright's staining method; The percentage of apoptotic cells was a time- and dose- dependent manner. STI571 and AS₂O₃ both could make K562 cells arrest in G₂/M phase, and the number of cells in G₁ phase and S phase decreases significantly; Typical DNA ladder was shown by DNA gel electrophoresis. Tyrosine phosphorylation levelsof Bcr-Abl, JAK2 and STAT5 were decreased in a time- and dose- dependent manner.Conclusion STI571 and As2O3 both could induce apoptosis of the K562 cells and inhibit its proliferation, the combination of the two drugs is better with the result. The mechanism of STI571 and AS2O3 inhibit proliferation of the K562 cells might be in connection with induce its apoptosis. The mechanism of STI571 and AS2O3 induce apoptosis of the K562 cells might be related to down-regulated expressions of Bcr-Abl in K562 cells, to interfere with the JAK-STAT signal transduction.