三氧化二砷增强硼替佐米、地塞米松对多发性骨髓瘤细胞的作用

目的 通过观察硼替佐米单用及与三氧化二砷(As_2O_3)、地塞米松(DXM)联合应用对多发性骨髓瘤(MM)细胞株KM3细胞增殖及凋亡的影响,探讨As_2O_3能否增强硼替佐米、DXM的抗MM作用.方法 采用MTT法检测硼替佐米单用及与As_2O_3、DXM联合应用对KM3细胞增殖的抑制作用,计算其IC_(50)值.采用细胞形态学、琼脂糖凝胶电泳检测DNA片段观察硼替佐米对KM3细胞凋亡的影响,Annexin V-FITC/PI染色流式细胞术检测硼替佐米联合As_2O_3、DXM后KM3细胞凋亡率的变化.结果 硼替佐米、As_2O_3及DXM对KM3细胞增殖抑制呈时间和浓度依赖性IC_(50)值分别为0.27、3.10、8.01 μmol/L;硼替佐米联合As_2O_3及DXM对KM3细胞的增殖抑制作用强于硼替佐米联合As_2_O3或DXM[(34.51±0.51)%对(25.39±0.90)%;(34.51±0.51)%对(23.80±0.78)%].0.25μmol/L硼替佐米与KM3细胞共孵育48 h后,KM3细胞出现典型的凋亡形态学改变,DNA电泳呈现梯形条带,Annexin V阳性细胞比例增高;硼替佐米联合As_2O_3、DXM组的KM3细胞凋亡率明显高于硼替佐米联合DXM组.结论 在体外,硼替佐米能够抑制KM3细胞增殖,诱导其凋亡.硼替佐米联合As_2O_3及DXM对KM3细胞增殖抑制作用显著增强;As_2O_3可增强硼替佐米、DXM对KM3细胞的诱导凋亡作用.

Arsenic trioxide enhances the effects of bortezomib, dexamethasone on multiple myeloma cell line KM3 in vitro

Objective To investigate the effect of bortezomib (Bor ) alone or in combination with As_2 0_3 (ATO) and/or dexamethasone (DXM) on proliferation and apoptosis in KM3 human multiple myeloma cell line KM3.Methods KM3 cells were cultured with different concentrations of Bor and ATO and/or DXM in combination or Bor、ATO、DXM alone for different times.Cell proliferation was assayed by MTT assay,and IC_(50) was calculated.Cell morphology was observed with light and electric microscopy.The agarose gel electro-phoresis was used to evaluate DNA content,and the flow cytometry was used to exam Annexin V-FITC/PI stain.Results Bor, ATO and DXM inhibited KM3 cell proliferation in a time-and dose-dependent manner with the IC_(50) of 0.27、3.10 and 8.01 μmol/L, respectively.The inhibition rate of KM3 cells by Bor plus ATO and DXM was significantly higher than Bor plus ATO or DXM [(34.51 ± 0.51) % vs (25.39 ± 0.90) % and (34.51 ±0.51)% vs (23.80 ±0.78)% respectively].Typical morphology for apoptosis and DNA ladder were observed in KM3 cell treated with 0.25 μmol/L Bor for 48 h, by Annexin V positivity.The apoptosis rate induced by Bor plus both ATO and DXM was higher than that induced by Bor plus DXM.Conclusion Bor can inhibit the proliferation and induce apoptosis of KM3 cells.Bor enhances the inhibitory effect of ATO and DXM on the growth of KM3 cell.ATO enhances the apoptosis effects of Bor and DXM on KM3 cells.