地西他滨增强allo-NK细胞杀伤白血病干细胞敏感性研究

发布时间：2018-06-17 04:53

本文选题：地西他滨 + 白血病干细胞　；参考：《中国实验血液学杂志》2017年01期

【摘要】：目的:探讨地西他滨增强allo-NK细胞杀伤白血病干细胞(LSC)的作用及其机制。方法:应用免疫磁珠法从KG1a细胞中分选LSC。从健康供者的外周血分离纯化同种异体反应性自然杀伤(allo-reactive natural killer,a1-Io-NK)细胞;LDH法检测allo-NK细胞对LSC的杀伤作用,流式细胞术检测allo-NK细胞诱导LSC凋亡及LSC表面NKG2D配体MICA/B和ULBP1-3的表达。结果:地西他滨10μmol/L处理LSC 24 h后,allo-NK细胞对LSC的杀伤率明显增高,在效靶比为5:1、10:1、20:1时分别为(60.52%±3.52%vs 22.08%±2.07%、73.93%±2.33%vs 28.99%±3.13%、83.08%±1.32%vs 36.44%±2.40%),差异有统计学意义(P0.05);地西他滨10μmol/L处理LSC 24 h后,在效靶比为10:1时,allo-NK细胞诱导LSC的凋亡率为7.84%±0.34%,明显高于LSC未处理组(3.33%±0.64%),差异有统计学意义(P0.05);地西他滨10μmol/L处理LSC 24 h后,LSC表面NKG2D配体(MICA/B、ULBP1、ULBP2、ULBP3)的表达上调,高于未处理组,差异有统计学意义(P0.05)。结论:地西他滨可能通过上调NKG2D配体增强allo-NK细胞对LSC的杀伤作用。
[Abstract]:Aim: to investigate the effect of dietabine on the killing of leukemia stem cells (LSCs) by allo-NK cells and its mechanism. Methods: LSCs were isolated from KG1a cells by immunomagnetic beads. The cytotoxicity of allo-NK cells to LSC was detected by LDH assay, and the apoptosis induced by allo-NK cells and the expression of NKG2D ligands MICA- / B and ULBP1-3 on LSC were detected by flow cytometry. Results: the cytotoxicity of allo-NK cells to LSC24 h after treatment with 10 渭 mol 路L 路L ~ (-1) of dicitabine was significantly higher than that of control group (60.52% 卤3.52%vs 22.08% 卤2.07% 卤2.073.93% 卤2.33%vs 28.99% 卤3.133.08% 卤1.32%vs 36.44% 卤2.405%) at the effective target ratio of 5: 1: 10: 1. The difference was statistically significant (P 0.05). The apoptosis rate of LSC induced by allo-NK cells at 10:1 was 7.84% 卤0.34, which was significantly higher than that of untreated LSC group (3.33% 卤0.64%), the difference was statistically significant (P 0.05), and the expression of NKG2D ligand MICA / BULBP1 ULBP2 ULBP3 on LSC was higher than that of untreated group after treatment with 10 渭 mol / L dietabine 10 渭 mol / L for 24 h. The difference was statistically significant (P 0.05). Conclusion: Dietabine may enhance the cytotoxicity of allo-NK cells to LSC by up-regulating NKG2D ligands.
【作者单位】：广东省人民医院(广东省医学科学院)血液科;湖北省荆门市第一人民医院血液内科;中山大学孙逸仙纪念医院肾内科;广东省人民医院(广东省医学科学院)病理生理研究室;
【基金】：国家自然科学基金(81370664) 广东省科技厅科技攻关计划项目(2013B021800188),广东省科技厅科技攻关计划项目(2013B021800094)
【分类号】：R733.71

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