NVP-BEZ235抑制CD34^+CD38^-急性髓系白血病干细胞的增殖和集落形成被引量：3

NVP-BEZ235 Inhibits Proliferation and Colony-forming Capability of CD34^+CD38^- Human Acute Myeloid Leukemia Stem Cells

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摘要本研究旨在探讨PI3K/mTOR信号系统双靶点抑制剂———NVP-BEZ235对CD34+CD38-髓系白血病干细胞增殖、细胞周期和集落形成能力的影响。用流式细胞术检测急性髓系白血病KG1a细胞表面CD34和CD38的表达;应用台盼蓝染色细胞计数法检测不同浓度NVP-BEZ235对KG1a细胞增殖的影响,PI染色流式细胞术检测NVP-BEZ235对KG1a细胞周期的影响,持续用软琼脂集落形成实验检测不同浓度NVP-BEZ235对KG1a细胞集落形成细胞的影响。结果表明,急性髓系白血病KG1a细胞中CD34+CD38-占(98.02±0.72)%,NVP-BEZ235(0.125-1μmol/L)对KG1a细胞增殖抑制呈现时间和剂量依赖(P<0.05),其24和48 h的IC50值分别为0.597和0.102μmol/L。0.5μmol/L的NVP-BEZ235作用24 h后,G0/G1期KG1a细胞比例达(83.2±3.80)%,较对照组(43.47±9.60)%明显增高(P<0.05)。2500个细胞在NVP-BEZ235(0-1μmol/L)持续作用下14 d和21 d而形成的集落数分别由375.67±21.46、706.33±87.31降至0(P<0.05)。结论:NVP-BEZ235能抑制CD34+CD38-髓系白血病干细胞增殖和集落形成。 This study was aimed to explore the effect of NVP-BEZ235, a dual phosphatidylinositol 3-kinase/ mammalian target of rapamycin inhibitor, on proliferation, cell cycle and colony forming capability of CD34＋ CD38 - human acute myeloid leukemia（AML） KG1a cells. Flow cytometry was used to detect expresstion of CD34 and CD38 on the surface of human AML KG1 a cells; Trypan blue assay was used to analyze the effect of NVP-BEZ235 at various concentrations on proliferation of KG1a ceils; flow cytometry was performed to examine the cell cycle of KG1a cells after NVP-BEZ235 treatment; Soft agar colony-forming experiment was used to detect the colony forming ability of KG1 a ceils treated with NVP-BEZ235 at various concentrations. The results indicated that the percentage of CD34＋ CD38- AML KG1a ceils was （98. 02 ± 0.72 ）%. NVP-BEZ235 （0. 125 - 1 μmol/L） inhibited the proliferation of KG1 a cells in a time-and dose-dependent manner （ P 〈 0.05 ） and the 50% inhibition concentrations （ ICs0 ） at 24 h and 48 h were 0. 597 μmol/L and 0. 102 μmol/L, respectively. KG1a cells were arrested at G0/G1 phase after treating with 0.5 μmol/L NVP-BEZ235 for 24 h, it was significantly higher than that of control group （ 83.2±3.80） % vs （43.47 ±9.60） % （P 〈0.05）. KG1a cells treated with NVP-BEZ235（0 - 1 μmol/L） for 14 d and 21 d, the number of colony decreased respectively from （ 375.67 ± 21.46） per 2500 KG1 a cells and （ 706.33± 87.31 ） per 2500 KG1 a cells to 0, with statistical significance （P 〈 0.05 ）. It is concluded that NVP-BEZ235 can inhibit proliferation and colony-forming capability of CD34 ＋ CD38 - human AML KG1a cells.

作者高莹莹胡亮杉韩慧娟宋朝阳黄宇贤郭坤元

机构地区南方医科大学珠江医院血液科广东省第二人民医院检验科

出处《中国实验血液学杂志》 CAS CSCD 北大核心 2013年第2期334-338,共5页 Journal of Experimental Hematology

基金国家自然科学基金(编号30973454) 广东省自然科学基金(编号S2012040007108)

关键词 NVP-BEZ235 CD34+CD38-KG1a细胞细胞周期集落形成 NVP-BEZ235 CD34＋ CD38 - KG1a cells cell cycle colony-forming capability

分类号 R733.71 [医药卫生—肿瘤] R979.1 [医药卫生—药品]

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