维甲酸、砷剂及柔红霉素对NB4细胞组织因子表达的影响  

Effects of all trans retinoic acid, arsenic trioxide and daunorubicin on tissue factor expression in NB4 cells

作　　者：郭为民[1] 诸江[1] 王鸿利[1] 赵维莅[1] 璩斌[1] 王学锋[1] 陈竺[1] 王振义[1] 

机构地区：[1]上海第二医科大学瑞金医院,上海血液学研究所,200025

出　　处：《中华血液学杂志》1999年第9期453-455,共3页Chinese Journal of Hematology

基　　金：胡应洲基金

摘　　要：目的　探讨全反式维甲酸（ Ａ Ｔ Ｒ Ａ） 、三氧化二砷（ Ａｓ２ Ｏ３） 及柔红霉素（ Ｄ Ｎ Ｒ） 对急性早幼粒细胞白血病（ Ａ Ｐ Ｌ） 细胞株 Ｎ Ｂ４ 细胞组织因子（ Ｔ Ｆ） 表达的影响。方法　用复钙时间检测 Ｎ Ｂ４ 细胞的促凝活性（ Ｐ Ｃ Ａ） ；用 Ｅ Ｌ Ｉ Ｓ Ａ 方法检测其 Ｔ Ｆ 抗原；用逆转录聚合酶链反应（ Ｒ Ｔ Ｐ Ｃ Ｒ） 检测 Ｔ Ｆｍ Ｒ Ｎ Ａ的转录水平。结果　 Ａ Ｔ Ｒ Ａ 和 Ａｓ２ Ｏ３ 均呈时间依赖的方式下调 Ｎ Ｂ４ 细胞的 Ｐ Ｃ Ａ、 Ｔ Ｆ 抗原水平以及 Ｔ Ｆ ｍ Ｒ Ｎ Ａ的转录；而 Ｄ Ｎ Ｒ 处理 Ｎ Ｂ４ 细胞的 Ｐ Ｃ Ａ及 Ｔ Ｆ 抗原在早期上调，至２４ ～４８ 小时达到最大值。对 Ｐ Ｃ Ｒ 产物测序，发现 Ａ Ｐ Ｌ 细胞 Ｔ Ｆ 第５ 个外显子缺失的转录本。结论　 Ａ Ｔ Ｒ Ａ 和 Ａｓ２ Ｏ３ 均可下调 Ａ Ｐ Ｌ 细胞 Ｔ Ｆ的表达并降低其 Ｐ Ｃ Ａ，改善 Ａ Ｐ Ｌ患者的弥散性血管内凝血（ Ｄ Ｉ Ｃ） 出血症状； Ａｓ２ Ｏ３ 和 Ｄ Ｎ Ｒ 对 Ａ Ｐ Ｌ凝血障碍不同效应的作用机制至少部分与药物对 Ａ Ｐ Ｌ细胞 Ｔ Ｆ 表达和 Ｐ Ｃ Ａ 的不同调节作用有关。Objective To investigate the effects of all trans retinoic acid(ATRA),arsenic trioxide(As 2O 3) and daunorubicin(DNR) on tissue factor(TF) expression in acute promyelocytic leukemia (APL) cell line NB4 cells. Methods Procoagulant activity(PCA) of NB4 cells treated with 1?μmol/L ATRA, 1?μmol/L As 2O 3 or 0.2?μg/ml DNR was detected using one stage clotting assay, TF antigen by ELISA,and TF mRNA by RT PCR. Results Both ATRA and As 2O 3 could down regulate the TF antigen, its mRNA transcription and membrane PCA of NB4 cells with a time dependent manner, while DNR was shown to increase these parameters. Moreover, by dideoxy sequencing of DNA fragment derived from PCR, it was found that there was a exon 5 deletion transcript of TF in APL cells.Its biological significance remained unknown.Conclusion TF expression and PCA of APL cells may be down regulated by ATRA and As 2O 3,therefore, As 2O 3 might also improve DIC related hemorrhage of APL while inducing APL cells to apoptosis. The distinct regulation of TF and PCA on APL cells by As 2O 3 and DNR may at least partially contribute to their effects on APL coagulopathy through the influence on coagulant factors activation.

关 键 词：维甲酸 砷剂 柔红霉素 白血病 APL 药物疗法 

分 类 号：R733.710.5[医药卫生—肿瘤]