Arsenic trioxide induces endoplasmic reticulum stress-related apoptosis in drug-resistant K562/ADM cells / 基础医学与临床

ABSTRACT

Objective To explore whether arsenic trioxide(As2O3)-induced apopotosis in drug-resistant leukemia K562/ADM cells may induce in through endoplasmic reticulum stress leukemia cell apopotosis.Methods The apoptosis of K562/ADM cells was identified by double staining of FITC-Annexin V and propidium iodide(PI),the ultrastructure of the cells,endoplasmic reticulum and mitochondria were observed by transmission electron microscopy.Flow cytometry(FCM) was employed to assess mitochondrial inner membrane potential(??m),intracellular calcium concentration,cytochrome c(Cyt c) release and caspase-3 activity.The expression of GRP78 protein was analyzed by Western blot.Results During the apoptotic process of K562/ADM cells induced with 2 ?mol/L and 5 ?mol/L As2O3,the endoplasmic reticulum exhibited obvious expansion and degranulation,and the mitochondria illustrated inner and outer membranes fusion,reduced and confused cristae,swelling and vacuolization.The mitochondrial ??m decreased,the intracellular calcium concentration and releasing of cytochrome c from mitochondria increased,and caspase-3 was activated.Western blot result indicated upregulation of GRP78 protein at endoplas-mic reticulum in apopototic K562/ADM cells.Conclusion As2O3 can initiate the endoplasmic reticulum stress in K562/ADM cells,and induces to apoptosis of the drug-resistant cell via endoplasmic reticulum-mitochondrial pathway.