基质细胞共培养对急性髓系白血病细胞耐药性影响及机制研究

发布时间：2018-05-02 19:23

本文选题：急性髓系白血病 + PIK/Akt信号通路　；参考：《中国实验血液学杂志》2017年02期

【摘要】：目的:研究基质细胞共培养对急性髓系白血病细胞耐药性的影响及机制。方法:将急性髓系白血病细胞HL-60与骨髓基质细胞HS-5共培养,用抗代谢药物阿糖胞苷(Ara-C)、蒽环霉素类药道诺霉素(DNR),生物碱类药物高三尖杉酯碱(HHT)对细胞进行联合处理,观察HL-60与HS-5共培养后对药物(DNR,HHT和Ara-C)敏感性的变化。同时用PI3K/AKT信号通路抑制剂LY294002处理细胞,研究共培养后细胞敏感性的变化与PI3K/AKT信号通路激活的相关性。结果:细胞抑制率的统计结果表明,HL-60与HS-5共培养后对药物的敏感性下降;mRNA定量和免疫蛋白印迹检测结果表明,HL-60与HS-5共培养后PI3K/AKT信号通路被激活,CCND1,FOXO1,PTEN等重要基因发生显著变化。结论:HL-60细胞通过与HS-5细胞共培养激活PI3K/AKT信号通路中的重要分子,如CCND1,FOXO1,PTEN,从而使HL-60细胞对药物的敏感性下降。
[Abstract]:Objective: to study the effect and mechanism of stromal cell co-culture on drug resistance of acute myeloid leukemia cells. Methods: acute myeloid leukemia cells (HL-60) and bone marrow stromal cells (HS-5) were co-cultured. The cells were treated with antimetabolite cytarabine Ara-CN, anthracycline DNRX and alkaloid homoharringtonine (HHT). The sensitivity of HL-60 and HS-5 to DNRHHT and Ara-Cwere observed. At the same time, the cells were treated with PI3K/AKT signal pathway inhibitor (LY294002) to study the relationship between the changes of cell sensitivity and the activation of PI3K/AKT signal pathway after co-culture. Results: the results of cell inhibition rate showed that the sensitivity of HL-60 to HS-5 was decreased after co-culture and the results of Western blot analysis showed that the signal pathway of PI3K/AKT was activated after co-culture with HS-5, and some important genes such as CCND1FOXO1PTEN were significantly changed. ConclusionThe sensitivity of HL-60 cells to drugs was decreased by co-culture with HS-5 cells to activate important molecules in the PI3K/AKT signaling pathway, such as CCND1, FOXO1, PTEN.
【作者单位】：郑州市第一人民医院血液肿瘤科;
【分类号】：R733.71

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