糖皮质激素对急性淋巴细胞白血病Puma表达的影响

Effect of glucocorticoid on the expression of Puma in acute lymphoblastic leukemia

摘要:

目的：糖皮质激素可通过调节某些基因的表达而诱导细胞凋亡,但在治疗白血病过程中对促凋亡蛋白Pum a表达的影响尚不清楚,该实验试探讨糖皮质激素在诱导体外培养的急性淋巴细胞白血病细胞凋亡过程中对Pum a表达的影响。方法：利用人急性淋巴细胞白血病细胞移植到免疫缺陷小鼠体内建立的细胞系,地塞米松处理后MTT比色法进行药物敏感性实验、W estern印迹及实时荧光定量PCR检测Pum a蛋白及mRNA的表达。结果：来源于临床疗效好的病例样本,其体外培养的白血病细胞对地塞米松敏感,来源于临床疗效差的病例样本,其体外培养的白血病细胞对地塞米松耐药,耐药组与敏感组白血病细胞间对地塞米松的体外敏感性有显著差异(P<0.05)。地塞米松处理后耐药组及敏感组均未见Pum a蛋白及mRNA的表达上调。结论：糖皮质激素在诱导体外培养的白血病细胞凋亡过程中,不能引起Pum a表达的上调。

Abstract:

OBJECTIVE: Glucocorticoid can induce apoptosis by regulating some genes' expression,but its effect on the pro-apoptotic protein Puma in leukemia remains unclear. This study was designed to investigate the effect of glucocorticoid on the expression of Puma in glucocorticoid-induced apoptosis of acute lymphoblastic leukemia cells in vitro. METHODS: Leukemia cells from acute lymphoblastic leukemia patients were transplanted into the immunodeficient mice. The transplanted leukemia cells were collected and then were treated with dexamethasone at the final concentration of 1 μM. The expression of Puma protein and mRNA in leukemia cells after dexamethasone treatment was detected by Western Blot and real-time quantitative PCR.A drug sensitive test was performed by MTT assay. RESULTS: The leukemia cells which came from the patients who had good clinical outcomes were sensitive to dexamethasone, while the ones from the patients who had poor clinical outcomes were resistant to dexamethasone in vitro. The sensitivity to dexamethasone in vitro between the resistant and sensitive leukemia cells was significantly different (P<0.05). No upregulation of Puma protein and mRNA was detected in resistant and sensitive leukemia cells after dexamethasone treatment. CONCLUSIONS: Glucocorticoid can not upregulate the expression of Puma in glucocorticoid-induced apoptosis of acute lymphoblastic leukemia cells in vitro.