摘要
目的探讨FLAG和IA方案对P-gp阳性和阴性急性髓细胞白血病（AML）细胞增生抑制作用的优劣及其机制。方法流式细胞仪检测K562和K562／A02细胞的P-gp表达，MTT法检测FLAG和IA方案对K562和K562／A02细胞的增生抑制作用，高效液相色谱法检测细胞内Ara-CTP、Ara-C水平，实时定量PCR检测细胞hENT1基因表达。结果K562和K562／A02细胞的P-gp阳性率分别为（1．32±0．24）％和（97．66±3．77）％，两种化疗方案对细胞的P-gp表达无影响。FLAG方案对K562细胞的增生抑制作用较IA方案差[（73．17±13．20）％对（84．41±9．33）％，P〈0．05]，而对K562／A02细胞的增生抑制作用优于IA方案[（70．55±11．32）％对（48．46±12．81）％，P〈0．01]。FLAG方案作用时AML细胞内Ara-CTP、Ara-C水平及人平衡核苷载体（hENT1）基因表达均较IA方案作用时升高（P〈0．05）。结论P-gp阳性AML细胞对FLAG方案较IA方案更敏感。氟达拉滨对Ara-C的生化调节可能是其主要机制。
Objective To explore in vitro effects and the mechanism for FLAG regimen compared with IA regimen in P-glyeoprotein-positive and -negative acute myeloblastic leukemia（AML） cell lines. Methods The expression of P-glycoprotein in K562 and K562/A02 cells were analyzed by flow cytometry. The effects of FLAG and IA on the proliferation of K562 and K562/A02 cells were detected by MTT assay. The Ara-CTP and Ara-C levels in those cells were measured by HPLC,the gene expression of bENT1 in K562 and K562/ A02 cells was detected by real-time PCR. Results The positive rates of P- glycoprotein were （1.32±0.24） % in K562 cell and （97.66±3.77） % in K562/A02 cell, respectively. The expression of P- glycoprotein had no change after treated with FLAG or IA. The cytotoxicity to K562 of IA was better than FLAG [（84.41±9.33） % v.s （73.17±13.20） %, P 〈0.05], and the cytotoxicity to K562/A02 of FLAG was better than IA [（70.55±11.32） % v.s （48.46±12.81） %, P 〈0.01]. Ara-C and Ara-CTP accumulation and bENT1 expression in AML cells treated with FLAG were higher than that treated with IA. Conclusion P-glycoprotein-positive AML cells are more sensitive to FLAG regimen than IA regimen. The biochemical modulation of Ara-CTP and Ara-C may be the major mechanism.
出处
《白血病．淋巴瘤》
CAS
2009年第2期69-71,共3页
Journal of Leukemia & Lymphoma
