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三氧化二砷与蛋白酶体抑制剂硼替佐米对Raji细胞系凋亡诱导的协同作用

[Synergistic effects of arsenic trioxide and proteasome inhibitor bortezomib on apoptosis induction in Raji cell line].

作者信息

He Yi, Yang Jian-Min, Wang Jian-Min, Zhou Hong, Lü Shu-Qing, Hu Xiao-Xia

机构信息

Department of Hematology, Changhai Hospital, The Second Military Medical University, Shanghai 200433, China.

出版信息

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2008 Aug;16(4):794-8.

Abstract

The aim of this study was to explore the synergistic effect of arsenic trioxide and bortezomib on apoptosis of Raji cell line. The cells were treated with arsenic trioxide, bortezomib, low-dose arsenic trioxide combined with bortezomib, respectively. The cell viability and proliferative curve were estimated by trypan blue dye exclusion. The cell apoptosis and cell cycle status were analyzed by flow cytometry. The apoptosis related elements such as caspase-3, BCL-2, BAX, JNK2 and IkappaB-alpha, were measured with Western blot. The results showed that compared with cells treated with mentioned above drugs alone, the proliferative potential of cells in combination group was significantly inhibited (p < 0.01), and apoptosis rate markedly increased (p = 0.001), while obvious cell cycle arrest was not observed. On the protein level, the expression of Caspase-3, BAX and IkappaB-alpha increased, while the expression of BCL-2, and JNK2 decreased. It is concluded that low-dose arsenic trioxide combined with bortezomib synergistically induced apoptosis in Raji cell line which may be mediated by inhibiting NK-kappaB and JNK2 signaling.

摘要

本研究旨在探讨三氧化二砷与硼替佐米对Raji细胞系凋亡的协同作用。分别用三氧化二砷、硼替佐米、低剂量三氧化二砷联合硼替佐米处理细胞。采用台盼蓝拒染法评估细胞活力和增殖曲线。通过流式细胞术分析细胞凋亡和细胞周期状态。用蛋白质免疫印迹法检测凋亡相关因子如半胱天冬酶-3、BCL-2、BAX、JNK2和IkappaB-α。结果显示,与单独使用上述药物处理的细胞相比,联合组细胞的增殖潜能受到显著抑制(p < 0.01),凋亡率明显升高(p = 0.001),但未观察到明显的细胞周期阻滞。在蛋白质水平上,半胱天冬酶-3、BAX和IkappaB-α的表达增加,而BCL-2和JNK2的表达降低。结论是,低剂量三氧化二砷联合硼替佐米可协同诱导Raji细胞系凋亡,其机制可能是通过抑制NK-κB和JNK2信号通路实现的。

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