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目的探讨阿糖胞苷(Ara-C)协同地塞米松(DEX)诱导糖皮质激素(GC)抵抗人类T淋巴细胞ALL细胞凋亡的效应及其临床意义。方法将不同水平的Ara-C(30 nmol.L-1、100 nmol.L-1、300 nmol.L-1)分别与不同浓度的DEX(100μmol.L-1、500μmol.L-1)联用对GC抵抗型Jurkat细胞进行不同浓度联合药物暴露。通过流式细胞计数检测各组细胞24 h、48 h暴露后凋亡率;ELISA法检测暴露24 h后核因子-κB(NF-κB)p65亚基活性;反转录-PCR(RT-PCR)和Western blot法检测暴露24 h后Survivin表达和蛋白水平。结果 Ara-C(100 nmol.L-1、300 nmol.L-1)与DEX(100μmol.L-1、500μmol.L-1)联合暴露组,其24 h和48 h暴露后细胞凋亡率均显著高于同浓度DEX单药暴露组(Pa<0.001),且呈显著浓度依耐性;联合暴露组NF-κB p65活性和Sur-vivin转录水平及蛋白水平较同浓度DEX单药暴露组均有显著下降(Pa<0.05)。结论 Ara-C与DEX具有显著的浓度依赖协同诱导GC抵抗型Jurkat细胞凋亡的作用,且这种协同效应可能是由于二者对NF-κB活性及其下游Survivin表达的协同抑制所产生的。
Objective To investigate the effect of dexamethasone (Ara-C) and dexamethasone (DEX) on glucocorticoid (GC) -induced apoptosis of human T lymphocyte ALL cells and its clinical significance. Methods Different levels of Ara-C (30 nmol.L-1, 100 nmol.L-1,300 nmol.L-1) and different concentrations of DEX (100μmol.L-1,500μmol.L-1) Different concentrations of co-administered drug were exposed to GC-resistant Jurkat cells. The apoptotic rate of each group was detected by flow cytometry at 24 h and 48 h after exposure. The activity of nuclear factor-kappaB (NF-κB) p65 subunit was detected by ELISA. The expression of NF- ) And Western blot were used to detect Survivin expression and protein level 24 h after exposure. Results After exposure to Ara-C (100 nmol.L-1,300 nmol.L-1) and DEX (100μmol.L-1,500μmol.L-1) for 24 h and 48 h, the apoptosis rate Were significantly higher than those in the same concentration DEX monotherapy group (Pa <0.001), and showed significant concentration dependence. The transcriptional level and protein level of NF-κB p65 and Survivin in co-exposure group were significantly higher than those in DEX monotherapy group There was a significant decrease (Pa <0.05). Conclusions Ara-C and DEX have a significant concentration-dependent synergistic effect on inducing apoptosis of GC-resistant Jurkat cells. This synergistic effect may be due to the synergistic inhibition of both NF-κB activity and downstream Survivin expression by Ara-C and DEX.