恶性造血细胞中P-gp 170表达的比较研究

摘要

目的:通过研究恶性造血细胞中P-糖蛋白(P-gp)170的表达,为骨髓增生异常综合征(MDS)治疗提供P-gp 170低表达的体外细胞株模型.方法:用含0.1 mmol·L-1阿霉素的RPMI 1640 分别培养MDS细胞株MUTZ-1和多药耐药(MDR)红白血病细胞株K562/A02.用MTT法检测细胞的增殖抑制作用,光镜和电镜技术分别观察与阿霉素共同培养后的MUTZ-1细胞和K562/A02细胞形态和超微结构,流式细胞仪分别测定MUTZ-1细胞和K562/A02细胞P-gp 170表达水平.结果:0.1 mmol·L-1阿霉素对MUTZ-1细胞增殖呈时间依赖性抑制作用,而对K562/A02细胞的增殖没有影响;MUTZ-1细胞出现典型的凋亡形态学改变,K562/A02细胞表面呈现出许多长的微绒毛和许多微孔;K562/A02细胞与MUTZ-1细胞相比高表达P-gp 170.结论:P-gp 170在恶性造血细胞中表达有显著性差异, P-gp 170低表达的MUTZ-1细胞株可用于MDS治疗的体外研究模型, P-gp 170高表达的K562/A02细胞株可用于MDR逆转的体外研究模型.%Objective To investigate the expression of P-glycoprotein(P-gp) 170 in malignant hematopoietic cells,and to provide a model with low expression of P-gp 170 in vitro suitable for myelodysplastic syndrome optimal therapy. Methods Myelodysplastic syndrome cell line(MUTZ-1) and a multidrug-resistance(MDR) erythroleukemia cell line(K562/A02) were cultured in medium of RPMI 1640 with 0.1 mmol·L-1adriamycin,respectively. The cell viability and cytotoxity were confirmed through MTT assay,the cell morphology was identified with optical microscope and observed under transmission electron microscope,and the P-gp 170 levels in MUTZ-1 and K562/A02 cells were detected by flow cytometry. Results 0.1 mmol·L-1adriamycin inhibited the proliferation of MUTZ-1 cells in a time-dependent manner and had no influence on K562/A02 cells; MUTZ-1 cells showed characteristic apoptotic morphology,while K562/A02 cells presented numerous long microvilli and lots of foramen and high expression of P-gp 170 as compared to sensitive MUTZ-1 cells. Conclusions Expression of P-gp 170 has remarkable difference in malignant hematopoietic cells. MUTZ-1 cell line is a suitable model for myelodysplastic syndrome optimal therapy in vitro,and K562/A02 cell line is a suitable model for studying the reversion of multidrug-resistance in vitro.