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Study on the mechanisms of cancer stem-like cells in multidrug-resistant K562 cells of insensitive to imatinib
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- Author:
- No author available
- Journal Title:
- JOURNAL OF LEUKEMIA & LYMPHOMA
- Issue:
- 5
- DOI:
- 10.3760/cma.j.issn.1009-9921.2006.05.005
- Key Word:
- K562多药耐药细胞系;肿瘤干细胞样细胞;伊马替尼;耐药机制
Abstract： 目的 进一步阐明一些高表达P-糖蛋白(P-gp)的慢性粒细胞白血病细胞对伊马替尼耐药的机制.方法 经过对K562细胞系长期的足叶乙苷(VP16)诱导和克隆筛选,建立一株耐药细胞系K562/VP16;利用干细胞高效能将Hoechst33342荧光染料泵出细胞的特性,采用流式细胞术,从K562/VP16细胞系中分选出一小群细胞,即边缘细胞(SP),称为K562/VP16 SP细胞,并初步探讨其抗伊马替尼的机制.结果 bcr/abl和abl蛋白在K562细胞、K562/VP16 SP细胞及非K562/VP16 SP细胞(non-SP K562/VP16)中的表达水平差异无统计学意义;P-gp在K562细胞中不表达,在K562/VP16 SP及non-SP K562/VP16细胞中均高表达且表达水平一致;与non-SP K562/VP16细胞比较,K562/VP16 SP细胞对伊马替尼的耐药性更强,并且这种抗性几乎不能被多种多药耐药逆转剂逆转;另外,体内外实验显示,K562/VP16细胞的致瘤性几乎全部来源于K562/VP16 SP细胞.结论 bcr/abl基因的扩增、过度表达和多药耐药基因及其蛋白表达产物P-gp的高表达,可能不是白血病细胞产生对伊马替尼临床耐药的重要机制;白血病细胞对伊马替尼具有一定的抗性,可能与数量极少的白血病干细胞有直接的关系.因此,这类数量极少的干细胞样的肿瘤细胞应当成为有效治疗肿瘤的靶细胞.
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