The Effects Of Total Astragalosides On The Mitochondria-dependent Apoptotic Pathway In NB4Cells

Acute leukemia (AL) is a malignant clonal disease of hematopoietic stem cells. A plenty of abnormal primitive cells and naive cells (leukemia cells) proliferate in the bone marrow and even inhibit the other organs such as liver, spleen, lymph nodes, so is a common clinical malignant diseases of the blood system.Acute promyelocytic leukemia (APL) is a special subtype of acute leukemia. The classical drugs for APL are ATRA and As2O3. As the milestone of leukemia treatment, they induce differentiation and apoptosis of promyelocytes, which led to disease remission. Nevertheless, adverse effects of those drugs make researchers try to develop new drugs which have better efficacy and little adverse effects. Our previous study showed that total astragalosides(TA) induced apoptosis of NB4cells, but mechanisms involved was still unknown. In this study, we explored the apoptosis mechanisms of NB4cells induced by TA with the hope for the development of new drugs.Objective:To study the effects of total astragalosides(TA) on the mitochondria-dependent apoptotic pathway in NB4cells.Methods: NB4cells were treated with different concentration (200、300、400ug/ml) of TA for48h. The rates of apoptosis of NB4cells and the expression of mitochondrial membrane potential were detected by flow cytometry. The mRNA expression of gene bcl-2and bax were detected by RT-PCR method. The relative activity of Caspase-3was examined by chromatometry assay.Results:1.After incubation for48h, there was significant difference in apoptosis between TA group and blank control(P<0.05). Besides,TA induced apoptosis of NB4cells in a dose-dependent manner. 2.Contrast with blank control,the expression of bcl-2mRNA mitochondrial membrane potential in TA groups were lower(P<0.05).3.There was no significant difference in the expression of bax mRNA between TA group and blank control.4.Contrast with blank control,the expression of mitochondrial membrane potential in TA groups were lower(P<0.05);5.Contrast with blank control,the activity of Caspase-3was higher(P<0.05).Conclusion: TA can induce apoptosis of NB4cells so has antileukemia effect in vitro. And TA may induce apoptosis of NB4cells by mitochondria-dependent pathway.