地西他濱增強(qiáng)allo-NK細(xì)胞殺傷白血病干細(xì)胞敏感性研究
發(fā)布時(shí)間:2018-06-17 04:53
本文選題:地西他濱 + 白血病干細(xì)胞; 參考:《中國(guó)實(shí)驗(yàn)血液學(xué)雜志》2017年01期
【摘要】:目的:探討地西他濱增強(qiáng)allo-NK細(xì)胞殺傷白血病干細(xì)胞(LSC)的作用及其機(jī)制。方法:應(yīng)用免疫磁珠法從KG1a細(xì)胞中分選LSC。從健康供者的外周血分離純化同種異體反應(yīng)性自然殺傷(allo-reactive natural killer,a1-Io-NK)細(xì)胞;LDH法檢測(cè)allo-NK細(xì)胞對(duì)LSC的殺傷作用,流式細(xì)胞術(shù)檢測(cè)allo-NK細(xì)胞誘導(dǎo)LSC凋亡及LSC表面NKG2D配體MICA/B和ULBP1-3的表達(dá)。結(jié)果:地西他濱10μmol/L處理LSC 24 h后,allo-NK細(xì)胞對(duì)LSC的殺傷率明顯增高,在效靶比為5:1、10:1、20:1時(shí)分別為(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%),差異有統(tǒng)計(jì)學(xué)意義(P0.05);地西他濱10μmol/L處理LSC 24 h后,在效靶比為10:1時(shí),allo-NK細(xì)胞誘導(dǎo)LSC的凋亡率為7.84%±0.34%,明顯高于LSC未處理組(3.33%±0.64%),差異有統(tǒng)計(jì)學(xué)意義(P0.05);地西他濱10μmol/L處理LSC 24 h后,LSC表面NKG2D配體(MICA/B、ULBP1、ULBP2、ULBP3)的表達(dá)上調(diào),高于未處理組,差異有統(tǒng)計(jì)學(xué)意義(P0.05)。結(jié)論:地西他濱可能通過(guò)上調(diào)NKG2D配體增強(qiáng)allo-NK細(xì)胞對(duì)LSC的殺傷作用。
[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% 鹵3.52%vs 22.08% 鹵2.07% 鹵2.073.93% 鹵2.33%vs 28.99% 鹵3.133.08% 鹵1.32%vs 36.44% 鹵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% 鹵0.34, which was significantly higher than that of untreated LSC group (3.33% 鹵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.
【作者單位】: 廣東省人民醫(yī)院(廣東省醫(yī)學(xué)科學(xué)院)血液科;湖北省荊門(mén)市第一人民醫(yī)院血液內(nèi)科;中山大學(xué)孫逸仙紀(jì)念醫(yī)院腎內(nèi)科;廣東省人民醫(yī)院(廣東省醫(yī)學(xué)科學(xué)院)病理生理研究室;
【基金】:國(guó)家自然科學(xué)基金(81370664) 廣東省科技廳科技攻關(guān)計(jì)劃項(xiàng)目(2013B021800188),廣東省科技廳科技攻關(guān)計(jì)劃項(xiàng)目(2013B021800094)
【分類(lèi)號(hào)】:R733.71
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