柔红霉素、地塞米松、全反式维甲酸对白血病细胞系CYP3 A5基因转录及活性的调控

Transcriptional and modulating activities of CYP3A5 gene induced by daunorubicin, dexamethasone and all-trans retinoic acid in some leukemia cell lines

目的 探讨化疗药对白血病细胞系CYP3A5基因转录及活性的调控。方法 采用RT -PCR、高压液相色谱法 (HPLC)检测药物干预后白血病细胞系CYP3A5基因的转录及活性。结果 K5 6 2 /A0 2细胞经柔红霉素作用后CYP3A5转录增强 ,HL -6 0 /ADR细胞则经诱导后出现CYP3A5转录。Jurkat细胞经地塞米松作用2 4h后出现微弱的CYP3A5转录 ,4 8h后转录明显增强。NB4细胞经全反式维甲酸作用 2 4～ 96h均诱导出现CYP3A5转录。K5 6 2细胞的CYP3A5活性显著高于HL- 6 0、NB4和Jurkat细胞。柔红霉素作用 2 4h后K5 6 2细胞的CYP3A5活性增高 ,4 8h后活性显著增高 ;而NB4和Jurkat细胞在柔红霉素作用 2 4h后CYP3A5活性无改变。地塞米松作用Jurkat细胞、全反式维甲酸作用NB4细胞均能诱导CYP3A5活性显著增高 ,并呈时间依赖性。结论 柔红霉素、地塞米松、全反式维甲酸的应用可诱导某些白血病细胞株CYP3A5基因的转录及活性。

Objective To investigate whether chemotherapeutic drugs can modulate the transcription and activities of CYP3A5 gene in some leukemia cell lines. Methods CYP3A5 mRNA and activities were detected in leukemia cell lines through RT-PCR and HPLC assay.Results Daunorubicin increased CYP3A5 mRNA level in K562/A02 cells and activated its transcription in HL-60/ADR cells. Dexamethasone induced a weak transcription of CYP3A5 gene after 24 hours and a strong transcription after 48 hours in Jurkat cells. All-trans retinoic acid activated transcription of CYP3A5 gene after 24 hours in NB4 cells. CYP3A5 activity of K562 cells was significantly statistically higher than those of HL-60, NB4 and Jurkat cells. Treatment with daunorubicin increased CYP3A5 activity after 24 hours in K562 cells, and further increased a statistically significant higher activity after 48 hours, whereas there were no remarkable changes in NB4 and Jurkat cell lines. Jurkat cells treated with dexamethasone and NB4 cells treated with all-trans retinoic acid had both significantly increased the CYP3A5 activities, and the induction was time-dependent. Conclusion Treatment with daunorubicin, dexamethasone and all-trans retinoic acid induce the transcription and modutating activity of CYP3A5 gene in some leukemia cell lines.