[1]王月莉,董 曼.磷脂酰肌醇-3激酶和组蛋白去乙酰化酶双靶点抑制剂CUDC-907对急性髓系白血病细胞体内、体外活性的影响[J].陕西医学杂志,2021,50(8):929-933.[doi:DOI:10.3969/j.issn.1000-7377.2021.08.007]
　WANG Yueli,DONG Man.Effect of PI3K and HDAC dual target inhibitor CUDC-907 on in-vitro and in-vivo activity of acute myeloid leukemia cells[J].,2021,50(8):929-933.[doi:DOI:10.3969/j.issn.1000-7377.2021.08.007]
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磷脂酰肌醇-3激酶和组蛋白去乙酰化酶双靶点抑制剂CUDC-907对急性髓系白血病细胞体内、体外活性的影响
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《陕西医学杂志》[ISSN:1000-7377/CN:61-1281/TN]

卷:
50
期数:
2021年8期
页码:
929-933
栏目:
基础研究
出版日期:
2021-08-05

文章信息/Info

Title:
Effect of PI3K and HDAC dual target inhibitor CUDC-907 on in-vitro and in-vivo activity of acute myeloid leukemia cells
作者:
王月莉; 董 曼
(铜川市人民医院血液科,陕西 铜川 727100)
Author(s):
WANG Yueli; DONG Man
(Department of Hematology,Tongchuan People's Hospital,Tongchuan 727100,China)
关键词:
急性髓系白血病;  磷脂酰肌醇-3激酶;  组蛋白去乙酰化酶;  CUDC-907;  生物学特性;  新靶点
Keywords:
Acute myelogenous leukemia;  PI3K;  HDAC;  CUDC-907;  Bionomics;  New target
分类号:
R 733.71
DOI:
DOI:10.3969/j.issn.1000-7377.2021.08.007
文献标志码:
A
摘要:
目的:探索磷脂酰肌醇-3激酶(PI3K)和组蛋白去乙酰化酶(HDAC)双靶点抑制剂CUDC-907对急性髓系白血病(AML)细胞体内、体外活性的影响及其作用机制。方法:首先采用Q-PCR法和Annexin V/PI双染色法探索CUDC-907对AML细胞株Kasumi-1和HL-60体外肿瘤细胞增殖、凋亡的影响以及相关蛋白的表达水平,然后采用上述方法探索CUDC-907对AML肿瘤移植免疫缺陷小鼠的骨髓细胞体内生物活性影响。结果:①Kasumi-1和HL-60细胞株的荧光强度、Mcl-1表达量高于正常人骨髓细胞,Bim低于正常人骨髓细胞,差异均具有统计学意义(均P<0.05); 使用2 μmol/L CUDC-907与未使用CUDC-907相比能降低Kasumi-1、HL-60 细胞的荧光强度、Mcl-1的表达水平,升高Bim表达水平,差异均具有统计学意义(均P<0.01); ②使用2 μmol/L CUDC-907处理AML细胞株Kasumi-1和HL-60与未使用CUDC-907相比双阴性细胞比例明显降低,差异均具有统计学意义(均P<0.01); ③与正常小鼠骨髓瘤细胞相比AML小鼠细胞荧光强度、Mcl-1的表达水平均显著升高,Bim降低,细胞增殖明显; 小鼠体内骨髓细胞经2 μmol/L CUDC-907处理后其增殖水平降低,其荧光强度和Mcl-1的表达水平低于未处理组,Bim升高,差异均具有统计学意义(均P<0.05); ④2 μmol/L CUDC-907处理AML小鼠细胞与未使用CUDC-907组相比双阴性细胞比例显著降低,差异均具有统计学意义(P<0.01)。结论:CUDC-907对AML细胞表现出明显的抑制细胞增殖和诱导其凋亡的作用,此为开发临床治疗AML的新靶点、新药物提供了实验依据。
Abstract:
Objective:To explore the effect of phosphatidylinositol-3 kinase(PI3K)and histone deacetylase(HDAC)dual target inhibitor CUDC-907 on the in-vivo and in-vitro activities of acute myeloid leukemia(AML)cells and the mechanism of action.Methods:Q-PCR and Annexin V/PI double staining were used to investigate the effects of CUDC-907 on in-vitro proliferation and apoptosis of AML cell line Kasumi-1 and HL-60,as well as the expression levels of related proteins.Then,the effects of CUDC-907 on the bioactivity of bone marrow cells from immune-deficient AML tumor transplantation mice were investigated by using these methods.Results:The fluorescence intensity and Mcl-1 expression of Kasumi-1 and HL-60 cell lines were higher than those of normal human bone marrow cells,and Bim was lower than that of normal human bone marrow cells(all P<0.05).The use of 2 μmol/L CUDC-907 reduced the fluorescence intensity of Kasumi-1 and HL-60 cells,the expression level of Mcl-1,and increased the expression level of Bim compared with non-use CUDC-907(all P<0.01).The ratio of double-negative cells in AML cell lines Kasumi-1 and HL-60 treated with 2 μmol/L CUDC-907 was significantly lower than that without CUDC-907(all P<0.01).Compared with normal myeloma cells,the fluorescence intensity and the expression level of MCL-1 in AML mouse cells were significantly increased,Bim was decreased,and cell proliferation was obvious; mice bone marrow cells after treated with 2 μmol/L CUDC-907 were significantly reduced,and the proliferation level was decreased,and the fluorescence intensity and the expression level of Mcl-1 was significantly lower than untreated group,and Bim increased(all P<0.05).The ratio of double-negative cells in AML mice treated with 2 μmol/L CUDC-907 was significantly lower than that in the non-CUDC-907 group(P<0.01).Conclusion:CUDC-907 can significantly inhibit cell proliferation and induce apoptosis on AML cells,which provides experimental evidence for the development of new targets and drugs for the clinical treatment of AML.

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备注/Memo

备注/Memo:
基金项目:陕西省卫生健康委员会科研基金资助项目(2018C008)
更新日期/Last Update: 2021-08-05