Xu Bo, Wang Bao-Jie, Li Ai-Min, Lock Richard
Faculty of Forensic Medicine, China Medical University, Shenyang 110001, China.
Zhongguo Dang Dai Er Ke Za Zhi. 2006 Apr;8(2):151-4.
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.
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 microM. 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.
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.
Glucocorticoid can not upregulate the expression of Puma in glucocorticoid-induced apoptosis of acute lymphoblastic leukemia cells in vitro.
糖皮质激素可通过调节某些基因的表达诱导细胞凋亡,但其对白血病中促凋亡蛋白Puma的影响尚不清楚。本研究旨在探讨糖皮质激素在体外诱导急性淋巴细胞白血病细胞凋亡过程中对Puma表达的影响。
将急性淋巴细胞白血病患者的白血病细胞移植到免疫缺陷小鼠体内。收集移植后的白血病细胞,然后用终浓度为1 microM的地塞米松进行处理。用地塞米松处理后,通过蛋白质免疫印迹法和实时定量聚合酶链反应检测白血病细胞中Puma蛋白和mRNA的表达。采用MTT法进行药敏试验。
临床预后良好患者的白血病细胞对地塞米松敏感,而临床预后较差患者的白血病细胞在体外对地塞米松耐药。耐药和敏感白血病细胞在体外对地塞米松的敏感性差异有统计学意义(P < 0.05)。地塞米松处理后,耐药和敏感白血病细胞中均未检测到Puma蛋白和mRNA的上调。
在体外糖皮质激素诱导急性淋巴细胞白血病细胞凋亡过程中,糖皮质激素不能上调Puma的表达。