骨髓基质细胞通过上调纤维连接蛋白介导白血病Jurkat细胞化疗耐药

发布时间：2018-05-01 07:16

本文选题：血液肿瘤 + 骨髓微环境　；参考：《华中科技大学学报(医学版)》2017年04期

【摘要】：目的探讨骨髓基质细胞通过上调纤维连接蛋白介导白血病Jurkat细胞化疗耐药。方法使用CCK-8法检测白血病Jurkat细胞对化疗药物吡柔比星的敏感性,绘制敏感曲线;体外建立Jurkat细胞与骨髓基质细胞(BMSC)共培养接触耐药模型,检测该模型中在吡柔比星作用下Jurkat细胞的抑制率,并检测在该模型中纤维连接蛋白(FN)的表达水平;体外建立Jurkat细胞与FN作用的粘附耐药模型,检测该模型中在吡柔比星作用下Jurkat细胞的抑制率;使用流式细胞仪检测在BMSC/FN耐药模型及单独培养模型中Jurkat细胞在吡柔比星作用下的凋亡率;收集复发难治血液肿瘤患者及正常人骨髓标本,检测标本上清中FN的水平。结果在与BMSC共培养接触耐药模型中,在相同浓度吡柔比星作用下,在同一时间点,Jurkat细胞凋亡率较单独培养组明显下降。在Jurkat细胞与BMSC共培养的接触耐药模型中,上清中分泌的FN明显上升。在FN作用的粘附耐药模型中,在相同浓度吡柔比星作用下,在同一时间点,Jurkat细胞凋亡率较单独培养组明显下降。与正常人比较,复发难治血液肿瘤患者骨髓上清中检测的FN水平明显上升。结论复发难治血液肿瘤患者的骨髓中,FN分泌增加;通过体外共培养模型提示骨髓基质细胞可以分泌FN,介导白血病Jurkat细胞发生化疗耐药,推测在白血病患者的骨髓微环境中,基质细胞可以为白血病细胞在化疗中提供耐药支持,黏附分子FN可能参与其中,是介导白血病细胞化疗耐药的重要原因。
[Abstract]:Objective to investigate the chemotherapeutic resistance of leukemic Jurkat cells mediated by bone marrow stromal cells up-regulated by fibronectin. Methods CCK-8 assay was used to detect the sensitivity of leukemia Jurkat cells to the chemotherapeutic drug pirarubicin and to draw a sensitive curve. The contact resistance model of Jurkat cells and bone marrow stromal cells (BMSCs) was established in vitro. The inhibition rate of Jurkat cells and the expression of fibronectin (FN) in the model were detected, and the adhesion resistance model of Jurkat cells to FN was established in vitro. The inhibition rate of Jurkat cells under the action of pirarubicin and the apoptosis rate of Jurkat cells under the action of pirarubicin in BMSC/FN resistant model and single culture model were detected by flow cytometry. Bone marrow samples were collected from patients with refractory hematological tumors and normal controls. FN levels in the supernatants were measured. Results in the model of drug resistance in co-culture with BMSC, the apoptosis rate of Jurkat cells in the same concentration of pirarubicin was significantly lower than that in the single culture group at the same time. In the contact resistant model of Jurkat cells co-cultured with BMSC, FN secreted in the supernatant increased significantly. In the model of adhesion resistance induced by FN, the apoptotic rate of Jurkat cells at the same time point in the same concentration of pirarubicin was significantly lower than that in the single culture group. The level of FN in bone marrow supernatant of patients with recurrent and refractory hematoma was significantly higher than that of normal controls. Conclusion the results suggest that bone marrow stromal cells can secrete FNs and mediate chemotherapeutic resistance of leukemic Jurkat cells in the bone marrow microenvironment of leukemia patients. Stromal cells can provide chemotherapeutic support for leukemia cells, and adhesion molecule FN may be involved in it, which is an important reason for the chemotherapeutic resistance of leukemia cells.
【作者单位】：湖北省肿瘤医院肿瘤内科;武汉市第五医院肿瘤科;华中科技大学同济医学院附属同济医院血液科;
【基金】：国家自然科学基金资助项目(No.30770913)
【分类号】：R733.7

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