摘要
目的探讨Hedgehog通路介导难治性髓系白血病(AML)生物学功能的影响。方法分别用浓度为0、10、50、100μmol/L的GANT-61处理人多药耐药的白血病HL60/ADR细胞株和放射抵抗的HL60/RX细胞株,采用CCK-8检测细胞增殖活性,流式细胞术检测细胞凋亡,克隆形成检测细胞存活,Western blot检测细胞表达。结果随着GANT-61浓度的增加与作用时间的延长,HL60/ADR与HL60/RX细胞的凋亡指数与细胞增殖抑制率显著提高,差异有统计学意义(P<0.05)。随着GANT-61浓度的增加与作用时间的延长,HL60/ADR与HL60/RX细胞的集落生成数目都显著降低,差异有统计学意义(P<0.05)。随着GANT-61浓度的增加与作用时间的延长,HL60/ADR与HL60/RX细胞的pAKT表达显著下降,NF-κB表达显著增加,差异有统计学意义(P<0.05)。结论Hedgehog通路可以通过调节PI3K/AKT/NF-κB途径,抑制难治性AML细胞的增殖,促进细胞调查,对临床治疗难治性AML提供一个潜在的有效方法。
Objective To investigate the effects of Hedgehog pathway on the biological function of refractory myeloid leukemia (AML).Methods The multidrug-resistant leukemia HL60/ADR cell lines and radioresistant HL60/RX cell lines were treated with GANT-61 concentration of 0、10、50、100μmol/L,respectively.The cell proliferation activity were detected by CCK-8,cell apoptosis were detected by flow cytometry,and the cell viability were detected by clone formation,the related protein expresion detected by the Western blot.Results With the increased of GANT-61 concentration and the prolongation of action time,the apoptosis index and cell proliferation inhibition rate of HL60/ADR and HL60/RX cells were increased significantly,and the compared difference were statistically significantly( P <0.05).With the increased of GANT-61 concentration and the prolongation of action time,the number of colony formation of HL60/ADR and HL60/RX cells were decreased significantly,and tthe compared difference were statistically significantly( P <0.05).With the increased of the concentration of GANT-61 and the prolongation of the action time,the expression of pAKT in HL60/ADR and HL60/RX cells decreased significantly,and the expression of NF-κB were increased significantly ( P <0.05).Conclusion Hedgehog pathway could inhibit the proliferation of refractory AML cells by regulating the PI 3K/AKT/NF-κB pathway,and promoting cell investigation.It provides a potential and effective method for clinical treatment of refractory AML.
作者
苗玉迪
李艳春
李庆瑞
Miao Yudi;Li Yanchun;Li Qingrui(The Blood Internal Medicine,Shaanxi People's Hospital,Shaanxi 710068,China)
出处
《医学研究杂志》
2019年第5期116-119,共4页
Journal of Medical Research
基金
中央级公益性科研院所基本科研业务专项资金资助项目(2016CS-69)