地西他滨联合安罗替尼对多发性骨髓瘤细胞增殖和凋亡的影响

Effects of Decitabine Combined with Anlotinib on Proliferation and Apoptosis of Multiple Myeloma Cells

目的:探讨地西他滨联合安罗替尼治疗多发性骨髓瘤(MM)的生物学效应及可能的机制。方法:分别应用不同浓度的地西他滨、安罗替尼以及地西他滨+安罗替尼处理MM细胞系和原代细胞,CCK-8法检测两药对细胞增殖的影响,并计算协同指数,流式细胞仪检测细胞凋亡率,Western blot检测药物对c-Myc蛋白的影响。结果:地西他滨和安罗替尼单药均能有效地抑制MM细胞系NCI-H929和RPMI-8226的增殖,并且诱导细胞凋亡;两药联合组抑制细胞增殖和诱导凋亡的效果明显强于单药组。两药联合在原代MM患者细胞中也显示出较强的细胞毒性。地西他滨和安罗替尼能够下调MM细胞中c-Myc蛋白的水平,并且联合用药组的c-Myc水平最低。结论:地西他滨联合安罗替尼能够有效地抑制MM细胞的增殖并且诱导其凋亡,这为地西他滨联合安罗替尼治疗MM提供了一定的实验基础。

Objective:To investigate the biological effects and its relative mechanism of decitabine combined with anlotinib on multiple myeloma cells.Methods:The human MM cell lines and primary cells were treated with different concentrations of decitabine,anlotinib,and decitabine+anlotinib,respectively.The cell viability was detected and combination effect was calculated by CCK-8 assay.The apoptosis rate was measured by flow cytometry and the level of c-Myc protein was determined by Western blot.Results:Both decitabine and anlotinib could effectively inhibit the proliferation and induce the apoptosis of MM cell lines NCI-H929 and RPMI-8226.The effect of combined treatment on the inhibition of cell proliferation and induction of apoptosis was stronger than that of single-drug treatment.The combination of the two drugs also showed strong cytotoxicity in primary MM cells.Decitabine and anlotinib could down-regulate the level of c-Myc protein in MM cells and the c-Myc level in the combination group was the lowest.Conclusion:Decitabine combined with anlotinib can effectively inhibit the proliferation and induce apoptosis of MM cells,which provides a certain experimental basis for the treatment of human MM.