Affect And Mechanisms Of Arsenic Trioxide-Induced Apoptosis In Human Multiple Myloma Cells

Object: Treatment of the acute promyelocytic leukemia with arsenic trioxide obtained prominent therapeutic effect in clinical work.At present, it has been used extensive. The main effect of treating tumor with arsenic trioxide included: inducing cell apoptosis; inducing tumor cells differentiation and suppressing cell growth. Arsenic apparently affects numerous intracellular signal transduction pathways, which include MAPK,JAK/STAT signal transduction pathways and Mitochondrial apoptosis pathway, and causes many alterations in cellular function. These actions of arsenic may result in the induction of apoptosis, the inhibition of growth and angiogenesis,and the promotion of differentiation. The abnormality of JAK1,ERK and bcl-2 signal transduction usually has the closely effect on the apoptosis of the tumor cells.Therefore, we have selected the JAK1,ERK and bcl-2 proteins as the study object, to investigate the Mechanism of arsenic trioxide on MM. This information will be critical to realizing the potential for its clinical use reasonably, thus providing enhanced benefit in cancer therapy.Methods: We selected multiple myloma RPMI8226 cell line which JAK1/STAT3 pathway is negative, the study object, detected the Inhibition rate through CCK8 method after the RPMI8226 cell was treated with different doses of ATO in 12h, 24h and 48h. We use fiuoreseenee flow Ceytometry (FCM) to detect the cell circles and apoptosis after treated with ATO for 48h at different concentrations.JAK1,ERK1/2 protein level and its phosphorylation level and bcl-2 protein leveel in RPMI8226 cells on different time through western blot. Studies have shown that ERK1/2 and phosphorylation ERK1/2 were expressed stably in RPMI8226 cells,and there no influence after the cell were treated with ATO.In order to study the mechanism of effect of arsenic trioxide on RPMI:8226 cells,we treated the RPMI8226 cells with 1-5 umol/L ATO for 48 hours .Later, we detected the bcl-2 protein level. The studies have shown that ATO induced the bcl-2 protein level down Regulation.Resaults:hese results verified that: 1. The ATO inhibited the RPMI8226cell in a dose-time dependent manner, and the dose larger,the time longer,the rate of inhibition was higher.The FCM show that ATO can induce RPMI8226 cell apoptosis and it inhibits the RPMI8226 cells in G1 phase. JAK1 is negative in RPMI8226 cell line. The ERK1/2 and Phosphorylation ERK1/2 were expressed stably in RPMI8226 cells.However,it has no change after the cells were treated with ATO.We find that ATO inhibits the proliferation of RPMI8226 cells through down regulated the level of Bcl-2. Conclusion: This study revealed that the mechanism of ATO induce the multiple myloma cells apoptosis, which has supplied the theoretical and experimental evidence for its clinical use. The mechanism of ATO on cancer is complicated.Multiple signal transduction pathways may have the effects. Recently, as the relation of cell apoptosis ans tumorigenesis was elucidated, we believe that ATO will play an important role in treatment of tumors.