三氧化二砷联合5-杂氮-2′-脱氧胞苷对U937细胞SHP-1、JAK3、TYK2基因表达的影响

张小坤; 罗建民; 孙 杰

doi:10.3971/j.issn.1000-8578.2014.07.009

三氧化二砷联合5-杂氮-2′-脱氧胞苷对U937细胞SHP-1、JAK3、TYK2基因表达的影响

1. 054000河北邢台，河北医科大学附属邢台市人民医院血液科；2.河北医科大学第二医院血液科血液病河北省重点实验室

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作者简介:
张小坤（1982-），女，硕士，主治医师，主要从事细胞内信号转导与恶性血液病的诊断与治疗

中图分类号: R733.71
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- 刊出日期: 2014-07-24

Effects of 5-Aza-2′-deoxycytidine Combined with Arsenic Trioxide on SHP-1, JAK3, TYK2 Expression in U937 Cells

1. Department of Hematology, Xingtai People's Hospital of Hebei Medical University, Xingtai 054000,China;2. Department of Hematology, The Second Hospital, Hebei Medical University

摘要

摘要: 目的探讨甲基化抑制剂5-杂氮-2′-脱氧胞苷（5-Aza-2′-deoxycytidine，5-aza-CdR）联合三氧化二砷（As2O3）对白血病细胞株U937中JAK3、TYK2和造血细胞磷酸酶SHP-1表达水平的影响，并探讨它们在白血病发病中的作用。方法 5-aza-CdR、As2O3单用及联合处理U937细胞，5-aza-CdR浓度为0.5、1、2 μmol/L，As2O3的浓度为1、2.5、5 μmol/L，As2O3 1μmol/L + 5-aza-CdR 0.5μmol/L、As2O32.5 μmol/L + 5-aza-CdR 1 μmol/L、As2O3 35 μmol/L + 5-aza-CdR 2 μmol/L 及不加药物组，分别处理24、48、72 h后提取细胞总RNA，荧光实时定量PCR（Real-time Quantitative Polymerase Chain Reaction，RQ-PCR）检测JAK3、TYK2 及SHP-1的表达。结果 As2O3和5-aza-CdR单独作用及两药合用时，SHP-1 mRNA在U937细胞中的表达呈剂量及时间依赖性，其表达逐渐升高；JAK3 mRNA的表达呈剂量及时间依赖性，其表达逐渐降低；TYK2 mRNA的表达呈剂量及时间依赖性，其表达逐渐降低；SHP-1与JAK3、TYK2负相关，JAK3所受影响较TYK2更为显著。结论（1）甲基化抑制剂5-aza-CdR和As2O3可使SHP-1表达升高，JAK3、TYK2表达降低，与浓度及作用时间有关。（2）SHP-1基因的重新表达与其发生去甲基化有关，对JAK/STAT通路有负调控作用。
- 甲基化抑制剂 /
- 5-杂氮-2′-脱氧胞苷 /
- SHP-1 /
- JAK3 /
- TYK2
Abstract: Objective To investigate the influence of methylation inhibitor of arsenic trioxide (As2O3) combined with 5-Aza-2′-deoxycytidine (5-aza-CdR) on the expression of JAK3, TYK2 and hematopoietic cell phosphatase SHP-1 in chronic myeloid leukemia cell line U937, and to explore the effects of the combination in leukemia pathogenesis. Methods 5-aza-CdR, As2O3 and the combined treatment were applied on U937 cells. As2O3 1 μmol/L and 5-aza-CdR 0.5μmol/L group, As2O3 2.5 μmol/L and 5-aza-CdR 1 μmol/L group, As2O3 5 μmol/L and 5-aza-CdR 2 μmol/L group and no chemical substances group were treated for 24, 48, 72 h, respectively. Then total cellular RNA was extracted. Real-time Quantitative PCR was used to detect the expression of JAK3, TYK2 and SHP-1. Results With the application of As2O3, 5-aza-CdR and the combination, SHP-1 mRNA expression in U937 cells was increased gradually, while JAK3 and TYK2 mRNA expression were decreased, in a dose- and time-dependent manner. SHP-1 was negatively correlated with JAK3 or TYK2. JAK3 was affected more obviously than TYK2. Conclusion (1) With the application of methylation inhibitor of As2O3 and 5-aza-CdR, the expression of SHP-1 was increased, while the expressions of JAK3 and TYK2 were decreased in a dose- and time- dependentmanner.(2)The reexpression of SHP-1 gene is related to its methylation and has a negative regulation role of JAK/STAT pathway.
- Methylation inhibitor /
- 5-Aza-2′-deoxycytidine /
- SHP-1 /
- JAK3 /
- TYK2

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参考文献(12)

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三氧化二砷联合5-杂氮-2′-脱氧胞苷对U937细胞SHP-1、JAK3、TYK2基因表达的影响

作者简介:
张小坤（1982-），女，硕士，主治医师，主要从事细胞内信号转导与恶性血液病的诊断与治疗

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Effects of 5-Aza-2′-deoxycytidine Combined with Arsenic Trioxide on SHP-1, JAK3, TYK2 Expression in U937 Cells

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三氧化二砷联合5-杂氮-2′-脱氧胞苷对U937细胞SHP-1、JAK3、TYK2基因表达的影响

作者简介: 张小坤（1982-），女，硕士，主治医师，主要从事细胞内信号转导与恶性血液病的诊断与治疗

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Effects of 5-Aza-2′-deoxycytidine Combined with Arsenic Trioxide on SHP-1, JAK3, TYK2 Expression in U937 Cells

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出版历程

目录

联系我们

作者简介:
张小坤（1982-），女，硕士，主治医师，主要从事细胞内信号转导与恶性血液病的诊断与治疗