Hedgehog信号通路抑制剂GANT61对急性髓系白血病细胞增殖和凋亡的影响  

Effect of hedgehog signaling pathway inhibitor GANT61 on the proliferation and apoptosis of acute myeloid leukemia

作　　者：孟腾腾[1] 魏虹[1] 管东方[1] 马翠[1] 吴广胜[2] 

机构地区：[1]石河子大学医学院组织学与胚胎学教研室,石河子832003 [2]石河子大学医学院第一附属医院血液风湿科,石河子832003

出　　处：《解剖学杂志》2017年第4期403-407,F0004,共6页Chinese Journal of Anatomy

基　　金：国家自然科学基金(81460024)

摘　　要：目的:探讨以Gli为靶点的hedgehog信号通路抑制剂GANT61对人急性早幼粒细胞白血病细胞HL-60增殖和凋亡的作用及机制。方法:采用CCK-8法观察不同浓度GANT61对HL-60细胞生长增殖的影响;Annexin V-FITC/PI双染检测GANT61对HL-60细胞凋亡的影响;RT-PCR检测48 h时HL-60细胞中gli1、bcl-2、bcl-xl mRNA表达;免疫荧光检测48 h时HL-60细胞中Gli1蛋白表达。结果:GANT61呈时间和浓度依赖性抑制HL-60细胞增殖;GANT61呈浓度和时间依赖性诱导HL-60细胞凋亡;GANT61呈浓度依赖性抑制gli1、bcl-2、bcl-xl mRNA表达;GANT61呈浓度依赖性抑制Gli1蛋白表达。结论:GANT61通过抑制Hedgehog-gli信号通路进而下调bcl-2和bcl-xl基因的表达,对人急性髓系白血病细胞HL-60起抑制增殖,并诱导其凋亡作用。Objective. To study the effect of Gli targeting hedgehog signaling pathway inhibitor GANT61 on the proliferation and apoptosis of acute early granulocyte leukemia cell HL-60. Methods： The effect of different concentrations of GANT61 on proliferation of HL-60 cells was examined by CCK-8 assay and the apoptosis rate was analyzed using Annexin V and PI double- staining. The expression levels of glil, bcl-2 and bcl-xl mRNA in HL-60 cells 48 h after the treatment were detected by RT- PCR. The expression of Glil protein of HL-60 cells was detected by immunofluorescence. Results： GANT61 was time and concentration dependent in terms of the inhibition of HL-60 cell proliferation. GANT61 was concentration and time-dependent in inducing the apoptosis of HL-60 cells. GANT61 demonstrated concentration-dependent inhibition of glil, bcl-2 and bcl-xl mRNA expression. GANT61 inhibited Glil protein expression in a concentration-dependent manner. Conclusion： GANT61 can inhibit the proliferation and induce the apoptosis of acute myeloid leukemia HL-60 cells by inhibiting the hedgehog-gli signaling pathway and downregulating bcl-2 and bcl-xl expression.

关 键 词：急性髓系白血病 GANT61 hedgehog-gli信号通路 细胞增殖 细胞调亡 

分 类 号：R733.7[医药卫生—肿瘤]