【摘要】 目的研究伊马替尼(IM)对T细胞Fyn、A20和NF-κB转录的影响及意义。方法 50 nmol/L浓度IM作用Jurkat细胞24 h后,以K562细胞为对照,应用实时荧光定量PCR技术检测Fyn、A20和NF-κB基因表达水平变化;Western blot技术检测A20和NF-κB蛋白水平变化。结果 IM明显上调Jurkat细胞A20基因表达水平,明显下调NF-κB基因表达水平,而Fyn基因表达水平没有明显变化。K562细胞受到IM处理后,A20和NF-κB的表达水平改变与Jurkat细胞相似,但Fyn基因水平明显下调。Fyn基因表达下调与IM下调BCR/ABL融合基因表达有显著的相关性。A20和NF-κB蛋白水平变化与mRNA变化一致。结论 IM不仅通过抑制BCR/ABL融合基因表达下调Fyn转录水平,而且也可通过上调A20和下调NF-κB表达抑制T细胞增殖作用。更多还原

【Abstract】 This study aimed to investigate the effects of Imatinib(IM) on the gene expression of Fyn,A20 and NF-κB in Jurkat cells and the significance of these gene expression changes.The Jurkat cells were stimulated by 50 nmol/L IM for 24 h,with K562 cells as control,and the gene expression levels of Fyn,A20 and NF-κB were detected by real-time fluorescence quantitative PCR.The relative changes of all gene expression were measured using 2-△△Ctformula;the changes of A20 and NF-κB protein expression in Jurkat cells were measured by Western blot.We found IM significantly upregulated the gene expression levels of A20 and downregulated the gene expression levels of NF-κB respectively in Jurkat cells,but the gene expression levels of Fyn does not change significantly;For K562 cells treated with IM,the gene expression of A20 and NF-κB is similar to Jurkat cells,but the gene expression levels of Fyn was significantly downregulated.The correlation of gene expression of Fyn and BCR/ABL were significant,and the expression leves of A20 and NF-κB protein consistented with that of mRNA.In conclusion,IM not only downregulate the gene level of Fyn by inhibiting BCR/ABL fusion gene,but also inhibit T cells proliferation by upregulating A20 and downregulating NF-κB gene expression.更多还原