摘要
目的:探讨核输出蛋白1(XPO1)抑制剂塞利尼索对急性髓系白血病(AML)Kasumi-1细胞增殖与凋亡的影响.方法:用MTS法检测不同浓度塞利尼索(0、2.5、5、10 μmol/L)作用于Kasumi-1细胞不同时间点(24、48、72 h)的增殖抑制率;流式细胞术检测不同浓度塞利尼索作用于Kasumi-1细胞48 h后的细胞凋亡率和细胞周期变化情况.结果:塞利尼索在不同时间点均可抑制Kasumi-1细胞生长,并呈浓度依赖(r24 h=0.7592,r48 h=0.9456,r72 h=0.9425);不同浓度塞利尼索均可抑制Kasumi-1细胞生长,并呈时间依赖(2.5 μmol/L组r=0.9057,5μmol/L组r=0.9897,10 μmol/L组r=0.9994).塞利尼索可诱导Kasumi-1细胞凋亡,且呈浓度依赖(r=0.9732),随着药物浓度的增大,诱导Kasumi-1细胞凋亡的作用越明显.塞利尼索作用于Kasumi-1细胞48 h后,G0/G1期细胞比例明显上升,S期细胞比例明显下降,并且随着塞利尼索药物浓度的增大,Kasumi-1细胞周期阻滞于G0/G1期的细胞比例增加,细胞合成减少.结论:塞利尼索可抑制Kasumi-1细胞增殖,诱导细胞凋亡,阻滞细胞周期于G0/G1期,导致肿瘤细胞的死亡.
Abstract
Objective:To investigate the effects of selinexor,a inhibitor of nuclear export protein 1(XPO1)on the proliferation inhibition and apoptosis of Kasumi-1 cells in acute myeloid leukemia(AML).Methods:MTS method was used to detect the inhibitory effect of different concentrations of selinexor on the proliferation of Kasumi-1 cells at different time points.The apoptosis rate and cell cycle changes after treatment with different concentration of selinexor were detected by flow cytometry.Results:Selinexor inhibited the growth of Kasumi-1 cells at different time points in a concentration-dependent manner(r24 h=0.7592,r48 h=0.9456,and r72 h=0.9425).Selinexor inhibited Kasumi-1 cells growth in a time-dependent manner(r=0.9057 in 2.5 µmol/L group,r=0.9897 in 5 μmol/L group and r=0.9994 in 10 μmol/L group).Selinexor could induce apoptosis of Kasumi-1 cells in a dose-dependent manner(r=0.9732),and the apoptosis of Kasumi-1 cells was more obvious with the increase of drug concentration.The proportion of G0/G1 phase was significantly increased and the proportion of S phase was significantly decreased after the treatment of Kasumi-1 cells by selinexor.With the increase of drug concentration,the proportion of Kasumi-1 cells cycle arrest in G0/G1 phase was increased and the cell synthesis was decreased.Conclusion:Selinexor can promote the death of tumor cells by inhibiting Kasumi-1 cells proliferation,inducing apoptosis and blocking cell cycle.
基金项目
福建省自然科学基金(2020J011303)
福建省自然科学基金(2020J011299)
福建省自然科学基金(2020J011302)
漳州市自然科学基金(ZZ2020J05)
漳州市医院博士工作室项目基金(PDA202103)
漳州市医院博士工作室项目基金(PDA202104)
漳州市医院博士工作室项目基金(PDB202110)
福建省卫健委科技计划项目(2023CXA053)
NETL
NSTL
万方数据