芒果苷对FLT3-ITD突变阳性急性髓系白血病细胞MV4-11增殖的影响及其机制研究

Effect of Mangiferin on Proliferation of FLT3-ITD Mutation Positive Acute Myeloid Leukemia Cell MV4-11 and Its Mechanism

目的:探讨芒果苷对FLT3-TD突变阳性急性髓系白血病细胞增殖、凋亡周期的影响及其机制。方法:应用CCK8法检测不同浓度芒果苷作用不同时间对MV4-11细胞增殖的影响;应用流式细胞术检测细胞凋亡、细胞周期及FLT3跨膜蛋白的表达;应用实时荧光定量聚合酶链反应(PCR)检测FLT3 mRNA的表达。结果:芒果苷对白血病细胞MV4-11具有明显抑制作用,且呈浓度效应关系(48 h,r=0.922;72 h,r=0.959;96 h,r=0.973);不同浓度芒果苷作用MV4-11细胞48 h时,观察到细胞周期内G0/G1期比率升高, S期比率下降,且随芒果苷浓度增高细胞凋亡越明显,IC50浓度芒果苷作用MV4-11细胞48 h后FLT3跨膜蛋白表达明显下降;qRT-PCR结果显示,芒果苷作用MV4-11细胞后FLT3mRNA表达明显降低(P<0.05)。结论:芒果苷可抑制MV4-11细胞增殖,阻滞细胞周期进程和促进细胞凋亡,其机制可能与芒果苷抑制FLT3活性继而影响下游与凋亡、增殖有关的信号传导通路有关。

Objective:To investigate the effects of mangiferin on proliferation,apoptosis and cycle of FLT3-ITD mutation-positive acute myeloid leukemia cells and its mechanism.Methods:The effects of different concentration of mangiferin on proliferation of MV4-11 cells were detected by CCK8 method.Apoptosis,cell cycle and FLT3 transmembrane protein expression were detected by flow cytometry.FLT3 mRNA expression was detected by real-time fluorescent quantitative polymerase chain reaction(PCR).Results:Mangiferin obviously inhibited MV4-11 proliferation in a concentration and time dependent manner(48 h,r=0.922;72 h,r=0.959;96 h,r=0.973).The ratio of G0/G1 phase in cell cycle increased with the enhancement of concentration of mangiferin in MV4-11 cells for 48 h,and the ratio of S phase decreased with enhasment of concentration.The increase of apoptosis was more obvious.The expression of FLT3 transmembrane protein significantly decreased after the actior of IC50 concentration of mangiferin in MV4-11 cells for 48 h.The results of qRT-PCR showed that the expression of FLT3 mRNA significantly decreased after treatment of MN4-11 cells with mangiferin(P<0.05).Conclusion:Mangiferin inhibits MV4-11 cell proliferation,arrests cell cycle progression and promotes apoptosis,which may be related with the inhibition of FLT3 activity by mangiferin and the subsequent signaling pathways involved in apoptosis and proliferation of cells.