Reversal effect of As_2O_3 on inhibition of apoptosis in multidrug-resistant K562/ADM cells

Objective To explore the molecular mechanisms of As2O3-induced apoptosis of multidrug-resistant leukemia K562/ADM cells. Methods The proliferating activity of K562/ADM cells was assessed by MTT assay. Cell apoptosis was determined by and annexinⅤ/PI double-staining. Expressions of mdr1, bcl-2 and caspase-3 mRNA were examined by reverse transcription polymerase chain reaction (RT-PCR). Expressions of bcl-2 protein and p-glycoprotein (P-gp) and caspase-3 activity were measured with FCM. Results As2O3 effectively inhibited the growth of K562/ADM cells. A typical apoptotic change was observed in K562/ADM cells after treatment with As2O3, and annexinⅤ/PI staining revealed an obvious increase in the apoptosis rate of the cells. the expressions of mdr1 and bcl-2 mRNA, P-gp and bcl-2 protein decreased while caspase-3 mRNA expression and caspse-3 activity markedly increased. Conclusions As2O3 induce apoptosis of drug-resistant K562/ADM cells. Its major molecular mechanism may be involved in the inhibitory effect of As2O3 on the expressions of mdr1 and bcl-2, and the reversal of inhibition of apoptosis in K562/ADM cells mediated by high expressions of P-gp and bcl-2.