Objective: To investigate the effect of arsenic sulfide (tetra-arsenic tetra-sulfide As4S4; diarsenic trisulfide As2S3) on tissue factor (TF) expression and procoagulant activity (PCA) of acute promyelocytic leukemia(...Objective: To investigate the effect of arsenic sulfide (tetra-arsenic tetra-sulfide As4S4; diarsenic trisulfide As2S3) on tissue factor (TF) expression and procoagulant activity (PCA) of acute promyelocytic leukemia( APL) cell lines ( NB4 and MR2) and the basic mechanism of their role. Methods: NB4 and MR2 cells were respectively treated with As4S4 , As2S3, As4S4 and Cyclohexamide( CHX). PCA of the cells was detected using one-stage clotting assay. TF antigen was detected by ELISA. TF and PML/RARa fusion gene mRNA by semi-quantitive RT-PCR. The PCA and TF antigen of HL-60 and K562 cells were also examined. Results: The PCA and TF antigen level in NB4 and MR2 cells were significantly higher than that in HL-60 and K562 cells. Both As4S4 and As2S3 can down-regulate the TF antigen , TF mRNA transcription and membrane PCA of NB4 and MR2 cells in vitro in a time-dependent manner. The role of As4S4 was stronger than that of As2S3. Both As4S4 and As2S3 had no effect on PML/RARa fusion gene transcription. CHX treatment completely suppressed the down-regulate effect of As4S4 on the TF mRNA expression. Conclusion: As4S4 and As2S3 may down regulate tissue factor expression and PCA of NB4 and MR2 cells. By down-regulating TF expression, As4S4 and As2S3 might be used to improve the DIC-related hemorrhage in APL patients. Elevated TF antigen level of NB4 and MR2 cells may be related to the fusion gene PML/RARa. The modulation of the TF mRNA expression in NB4 and MR2 cells by As4S4 and As2S3 might be indirect and might not involve PML/RARa fusion gene.展开更多
基金Supported by Chinese Medicine Foundation of Shaanxi Province(No.1999002)
文摘Objective: To investigate the effect of arsenic sulfide (tetra-arsenic tetra-sulfide As4S4; diarsenic trisulfide As2S3) on tissue factor (TF) expression and procoagulant activity (PCA) of acute promyelocytic leukemia( APL) cell lines ( NB4 and MR2) and the basic mechanism of their role. Methods: NB4 and MR2 cells were respectively treated with As4S4 , As2S3, As4S4 and Cyclohexamide( CHX). PCA of the cells was detected using one-stage clotting assay. TF antigen was detected by ELISA. TF and PML/RARa fusion gene mRNA by semi-quantitive RT-PCR. The PCA and TF antigen of HL-60 and K562 cells were also examined. Results: The PCA and TF antigen level in NB4 and MR2 cells were significantly higher than that in HL-60 and K562 cells. Both As4S4 and As2S3 can down-regulate the TF antigen , TF mRNA transcription and membrane PCA of NB4 and MR2 cells in vitro in a time-dependent manner. The role of As4S4 was stronger than that of As2S3. Both As4S4 and As2S3 had no effect on PML/RARa fusion gene transcription. CHX treatment completely suppressed the down-regulate effect of As4S4 on the TF mRNA expression. Conclusion: As4S4 and As2S3 may down regulate tissue factor expression and PCA of NB4 and MR2 cells. By down-regulating TF expression, As4S4 and As2S3 might be used to improve the DIC-related hemorrhage in APL patients. Elevated TF antigen level of NB4 and MR2 cells may be related to the fusion gene PML/RARa. The modulation of the TF mRNA expression in NB4 and MR2 cells by As4S4 and As2S3 might be indirect and might not involve PML/RARa fusion gene.
