| Objective:(1)To investigate the regulatory effects of Anidulafungin(ANI)on the cell viability and proliferation of chronic myeloid leukemia cells and the underlying molecular mechanisms;(2)To explore the combined effect and mechanism of anidulafungin and imatinib in chronic myeloid leukemia cells.Methods: K562,Jurkat and U937 cells were treated with anidulafungin and micafungin at different concentrations,and cell viability was detected by CCK8 assay.The proliferation ability of cells was detected by soft agar clone formation assay.Annexin V/PI flow cytometry,Caspase-3 activity detection kit and the expression levels of apoptosis-related proteins BCL-2,BAX and Caspase-3 by Western Blot were used to comprehensively analyze the apoptosis.Western Blot was used to analyze the effects of anidulafungin,imatinib and their combination on p-BCR/ABL,BCR/ABL,p-STAT5 and STAT5 protein levels.Western Blot was used to detect the effects of anidulafungin,anidulafungin plus autophagy inhibitor Bafilomycin A1(Baf A1)on the expression levels of autophagy related proteins LC3 and p62.K562 cells were treated with Caspase inhibitor Z-VAD-FMK combined with anidulafungin,and cell viability was analyzed by CCK8 assay.Results: CCK8 and soft agar cloning experiments showed that anidulafungin could inhibit cell viability and proliferation of K562 cells in a dose-dependent and time-dependent manner.Moreover,anidulafungin can promote the anti-chronic myeloid leukemia effect of imatinib.Annexin V/PI flow cytometry,Caspase-3 activity assay and Western Blot results showed that anidulafungin could induce apoptosis and autophagy in K562 cells.Western Blot results showed that anidulafungin could down-regulate p-BCR/ABL,BCR/ABL,p-STAT5 and STAT5 protein levels alone or in combination with imatinib.Conclusion: Anidulafungin may play an anti-chronic myeloid leukemia role by regulating BCR/ABL-STAT5 signaling pathway,and may promote the anti-chronic myeloid leukemia effect of imatinib.Figures 8,tables 10,references 83... |
