Characterization of a stem cell population in lung cancer A549 cells
Characterization of a stem cell population in lung cancer A549 cells
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DOI：
10.1016/j.bbrc.2008.04.038
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发表时间：
2008-06-20
影响因子：
3.1
通讯作者：
Shin, Ho-Chul
中科院分区：
文献类型：
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作者：
Sung, Ji-Min;Cho, Hee-Jung;Shin, Ho-Chul
我们使用FACS/Hoechst 33342从人肺癌A549细胞中分离出一个干细胞亚群。该侧群（SP）占总细胞群的24%，在选择性abcg2抑制剂fumitremorgin c处理后完全消失。在一项重新种群研究中，分离的SP和非SP细胞都能产生SP和非SP细胞的异质种群，但SP细胞的重新种群发生得比非SP细胞更快。MTT试验和细胞周期分布分析显示SP组和非SP组之间具有相似的特征。然而，在多柔比星（DOX）和甲氨蝶呤（MTX）存在下，SP细胞的Annexin V染色明显低于非SP细胞。综上所述，这些结果表明，与非SP细胞相比，SP细胞具有活跃的再生能力和较高的抗凋亡活性。此外，我们的基因芯片(R)数据显示，ABCG2和ABCC2的mRNA表达在SP细胞中升高。总的来说，这些数据解释了为什么A549的SP具有独特的抵抗DOX和MTX治疗的能力。因此，我们认为ABCG2转运体的表达在A549 SP细胞的多药耐药表型中起重要作用。(C) 2008爱思唯尔公司版权所有。
We isolated a stem cell subpopulation from human lung cancer A549 cells using FACS/Hoechst 33342. This side population (SP), which comprised 24% of the total cell population, totally disappeared after treatment with the selective ABCG 2 inhibitor fumitremorgin C. In a repopulation study, isolated SP and non-SP cells were each able to generate a heterogeneous population of SP and non-SP cells, but this repopulation occurred more rapidly in SP cells than non-SP. An MTT assay and cell cycle distribution analysis reveal a similar profile between SP and non-SP groups. However, in the presence of doxorubicin (DOX) and methotrexate (MTX), SP cells showed significantly lower Annexin V staining when compared to non-SP cells. Taken together, these results demonstrate that SP cells have an active regeneration capacity and high anti-apoptotic activity compared with non-SP cells. Furthermore, our GeneChip (R) data revealed a heightened mRNA expression of ABCG2 and ABCC2 in SP cells. Overall these data explain why the SP of A549 has a unique ability to resist DOX and MTX treatments. Therefore, we suggest that the expression of the ABCG2 transporter plays an important role in the multidrug resistance phenotype of A549 SP cells. (C) 2008 Elsevier Inc. All rights reserved.