维甲酸和三氧化二砷下调NB4细胞组织因子表达的作用机制  

Mechanism of tissue factor expression on NB4 cells down regulated by all-trans retinoic acid and arsenic trioxide

作　　者：郭为民[1] 王鸿利[1] 赵维莅[1] 璩斌[1] 潘玲 诸江[1] 储海燕[1] 王学锋[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》2000年第5期240-243,共4页Chinese Journal of Hematology

基　　金：胡应洲基金

摘　　要：目的　研究全反式维甲酸 (ATRA)和三氧化二砷 (As2 O3)下调NB4细胞组织因子 (TF)表达的作用机制。方法　用放线菌酮抑制蛋白合成和用放线菌素D阻断RNA合成后 ,用逆转录 聚合酶链反应 (RT PCR)检测ATRA对NB4细胞TFmRNA转录的影响。将含有PML RARα融合蛋白全部编码序列的重组逆转录病毒质粒转染U937细胞 ,以转染空载体的U937细胞为对照 ,用ELISA方法检测ATRA和As2 O3处理的转染PML RARαU937细胞的TF抗原。结果　放线菌酮完全阻断了ATRA对NB4细胞TFmRNA的下调作用 ;ATRA使NB4细胞的TFmRNA的半寿期从正常对照的 6 0min缩短至 30min。转染PML RARα的U937细胞与转染逆转录病毒载体的U937细胞相比 ,其TF表达水平显著升高(P <0 .0 1) ;使用ATRA或As2 O3分别处理转染PML RARα的U937细胞和对照细胞 2 4h ,ATRA和As2 O3均可显著地降低这两个细胞株的TF抗原水平。结论　ATRA对NB4细胞TFmRNA的下调作用依赖于新的蛋白质合成 ,ATRA可能是以间接方式下调APL细胞TFmRNA的转录 ;ATRA处理的NB4细胞TFmRNA的稳定性也有所降低。APL细胞染色体易位产生的融合蛋白PML RARα可能对TF的异常表达有一定的影响。ATRA和As2 O3对TF的下调作用可能不依赖于融合蛋白PMLObjective To investigate molecular mechanism of tissue factor (TF) expression on acute promyelocytic leukemia cell line NB4 cells down regulated by all trans retinoic acid (ATRA) and arsenic trioxide (As 2O 3). Methods Cyclohexamide (CHX) inhibition test for de novo protein synthesis and actinomycin D (Act D) inhibition test for RNA synthesis were used to check the effect of ATRA on the TF expression. TF antigen of U937 cells transfected with pMSCV PML RARα treated with or without ATRA and As 2O 3 was detected. Results CHX treatment completely suppressed the down regulation effect of ATRA on the TF mRNA expression, Act D inhibition test showed that half life of TF mRNA in treated NB4 cells was shortened to about 30 min from that of around 60 min in untreated NB4 cells. The TF antigen contents in U937 cells transfected with pMSCV PML RARα were significantly higher than that in transfected U937 cells with retrovirus vector. Both ATRA and As 2O 3 could down regulate the TF antigen level in U937 cells transfected with or without PML RARα. Conclusion The modulation of the TF mRNA expression in NB4 cells by ATRA might be indirect. TF mRNA destabilization was involved in the TF regulation process mediated by ATRA. Elevated TF antigen level in U937 cells transfected with pMSCV PML RARα may be related to the fusion protein PML RARα. The down regulation effect of ATRA and As 2O 3 on the TF expression of U937 cells might not involve the fusion protein.

关 键 词：维甲酸 白血病 APL 组织因子 三氧化二砷 治疗 

分 类 号：R730.2[医药卫生—肿瘤]