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急性早幼粒白血病细胞ATRA耐药株HL-60R、NB4R的构建及鉴定
作者:张亚芬  张莹  缪凤琴  张建琼 
单位:东南大学医学院 病原生物学与免疫学系, 发育与疾病相关基因教育部重点实验室, 江苏 南京 210009
关键词:急性早幼粒细胞白血病 全反式维甲酸 多药耐药 HL-60R NB4R 
分类号:R-33;R733.71
出版年·卷·期(页码):2014·33·第五期(569-572)
摘要:

目的:构建急性早幼粒细胞白血病细胞系HL-60、NB4的全反式维甲酸耐药株HL-60R、NB4R,并对其生物学性状进行鉴定。方法:以全反式维甲酸(ATRA)为诱导药物,采用浓度递增间歇诱导法构建HL-60、NB4细胞相应的ATRA耐药株。CCK8法鉴定其ATRA耐药性,并检测耐药细胞株的生长曲线及多药耐药性。结果:成功构建了ATRA耐药细胞株HL-60R、NB4R,并发现与亲代细胞相比,其生长增殖速度减慢,群体倍增时间延长,且对其它多种化疗药物产生一定程度的交叉耐药。结论:成功构建的耐药细胞系HL-60R、NB4R为急性早幼粒细胞白血病多药耐药机制的进一步研究奠定了基础。

Objective: To establish human acute promyelocytic leukemia (APL) ATRA-resistant cell lines and to explore their biological characteristics. Methods: Human APL ATRA-resistant cell lines HL-60R and NB4R were established by stepwise increasing concentrations of ATRA selection from the parental cell lines HL-60 and NB4.Drug sensitivity of resistant cells was detected by CCK8 assay,and the changes of biological characteristics were determined by light microscopy and cell counting. Results: Human APL ATRA-Resistant cell lines HL-60R and NB4R were developed with stable resistance to ATRA.Compared to parental cells,HL-60R and NB4R cells grew more slowly and had a longer doubling time. Besides,HL-60R and NB4R cells exhibited cross-resistance to etoposide, vincristine sulfate, cytarabine and doxorubicin. Conclusion:HL-60R and NB4R cells are reliable multi-drug resistant cell sublines of APL.The successful establishment of these cells has laid a solid foundation for further study of the multi-drug resistant mechanism of human APL induced by ATRA.

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