耐药调节剂对急性髓系白血病细胞株CYP3A5基因转录及蛋白表达影响

Role of multidrug resistance moderator in the transcription and translation of CYP3A5 in acute myelocytic leukemia cell lines

目的:探讨耐药调节剂对急性髓系白血病细胞株(急髓细胞株)细胞色素P450 3A亚家族多肽5(CYP3A5)转录及蛋白表达的影响及其与白血病耐药的关系。方法:采用RT-PCR和Western印迹法检测药物代谢酶CYP3A5转录和蛋白表达水平。结果:K562、U937细胞经环孢素作用24h后CYP3A5转录增强,维拉帕米则出现微弱的转录,作用48h后两者转录均减弱,与未加药细胞组相比差异有统计学意义(P<0.01);K562细胞经环孢素、维拉帕米作用24～48h后,蛋白表达均增加,与未加药细胞组相比差异有统计学意义(P<0.01);U937细胞蛋白表达与基因转录基本一致。结论:耐药调节剂可诱导急髓细胞株CYP3A5基因的转录和蛋白的表达。

Objective To investigate the role of muhidrug resistance moderator in regulating CYP3A5 gene expression in acute myelocytic leukemia （AML） cell lines. Methods The mRNA and protein expression of CYP3A5 in AML cell lines were detected by RT-PCR and Western Blot. Results Compared with control, CYP3A5 mRNA was upregulated after 24 hours exposure to Cyclosporine A . In contrast, Verapamil induced a faint CYP3A5 mRNA expression after 24 hours exposure （P〈0.01）. The efficacy of transcriptional regulation of both agents was progressively weakened after 48 hours. CYP3A5 protein was upregulated in K562 cell after 24 to 48 hours exposure to cyclosporine A and verapamil （P〈0.01）. The protein level of CYP3A5 was concomitant with that of mRNA level in U937 cell. Conclusions The transcription and translation of CYP3A5 gene in AML cell lines could be induced by muhidrug resistance moderator.