Interference Of Arsenic Trioxide And Dexamethasone In Proliferation Of Multiple Myeloma Cell Promoted By SDF-1

Objective: At present,study indicated that the growth,survival and drug resistance of multiple myeloma (MM) was deeply related to hematopoietic microenviroment.Many kinds of drugs chemotherapy and/or transplantation of hemato-poietic stem cell and support therapy,which to evidently heighten catabatic rate of the patients of multiple myeloma , but the multiple myeloma still threaten the health of patients severely.So,study the mechanism of MM, discuss the factors stimulate the proliferation of MM cells in marrow microenviroment, observe its influence factors and find out effective drugs would provide new study way and method to the mechanism and treatments for MM . SDF-1 is secreted by bone marrow stromal cell,combine with CXCR4 receptor and form the axes of SDF-1 /CXCR4,play an important role in the survival,proliferation,adherence, migration and homing of leukemia cells , and also in the proliferation and differentiation of MM cells.In our studying,take the MM cells as the target cells, observe the influence of Dexa methasone (DEX) and Arsenic Trioxide(AS2O3) on growth of MM cells with the exist of SDF-1.Method:(1)Detected the influence of SDF-1,DEX and AS2O3 on RPMI8226 cells by MTT.(2)Described the growth curve by MTT method,and observe the effect of SDF-1 and DEX and/or AS2O3 with/or without the exist of SDF-1 on the growth curve of MM cells.(3)Detected the effect of SDF-1 and / or DEX and / or AS2O3 on the change of RPMI8226 cells cycle by FCM. Eight groups were set up, SDF-1, DEX,DEX+ SDF-1, AS2O3, AS2O3+SDF-1,DEX+AS2O3,DEX+AS2O3+SDF-1 and control group.Result:1,Result of MTT: (1) SDF-1(2×103pg/ml) could accelerated the proliferation of RPMI8226 MM cells in 48 hours in vitro, the average proliferation rate was (24.3±2.3)%.(2) The growth of MM cells were inhibited in DEX group or AS2O3 group with the exist of SDF-1.(3) The inhibition rate of DEX and AS2O3 group was higher than DEX group or AS2O3 group with or without SDF-1, there was statistical difference in these groups(P<0.05). The inhibition rate of DEX and AS2O3 group with SDF-1 was higher than DEX group or AS2O3 group without SDF-1, there was statistical difference in these groups(P<0.05). (4) The inhibition rate of DEX group and AS2O3 group with SDF-1 was lower than each of them without SDF-1.2,Detected the cycle of MM cells:(1)The proportion of cells in G0/G1 periods in SDF-1 group was lower than the control group, but the proportion of cells in S periods in SDF-1 group was higher compare with the control group,there was statistical difference between the two groups(P<0.05).(2) The proportion of cells in G0/G1 periods in DEX group and AS2O3 group with the exist of SDF-1 was higher than the SDF-1 group, but the proportion of cells in S periods was lower compare with the SDF-1 group,there was statistical difference between these groups(P<0.05).(3) The proportion of cells in G0/G1 periods in DEX and AS2O3 group was higher than the DEX group and AS2O3 group with/or without the exist of SDF-1, but the proportion of cells in S periods was lower compare with the latter two groups,there was statistical difference between these groups(P<0.05). The proportion of cells in G0/G1periods in DEX and AS2O3 group with SDF-1 was higher than the DEX group and AS2O3 group without SDF-1 ,there was statistical difference between these groups(P<0.05). (4) The proportion of cells in G0/G1 periods in DEX group and AS2O3 group with the SDF-1 was lower than each group without the SDF-1, but the proportion of cells in S periods was higher compare with the latter two groups,there was statistical difference between these groups(P<0.05).Conclusion:SDF-1 is an important factor that promote the proliferation of MM cells in marrow microenviroment. DEX or AS2O3 can inhibit the growth of MM cells proliferated by SDF-1. The inhibition effect to MM cell of DEX combine with AS2O3 whether exists the DSF-1, it seems to be positive cooperative of them. DEX combine with AS2O3 can eliminate the effect of SDF-1 when the level of SDF-1 is high.SDF-1 can reduce the sensitivity of MM cells to DEX and AS2O3. AS2O3 can inhibit the MM cells.