Arsenic Trioxide overcomes cell adhesion-mediated drug resistance through down-regulating the expression of β1-integrin in K562 chronic myelogenous leukemia cell line
Arsenic Trioxide overcomes cell adhesion-mediated drug resistance through down-regulating the expression of β1-integrin in K562 chronic myelogenous leukemia cell line
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DOI：
10.3109/10428191003746315
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发表时间：
2010-06-01
影响因子：
2.6
通讯作者：
Lu Yue
中科院分区：
文献类型：
--
作者：
Wang Guo-Bao;Chen Xiao-Qin;Lu Yue
骨髓微环境保护白血病细胞免受药物损伤，细胞粘附介导的耐药（CAM DR）是骨髓微小残留病根除的主要障碍。在这项研究中，我们评估了K562细胞与慢性粒细胞白血病（CML）患者骨髓基质细胞（BMSCs）共培养的存活反应。与悬浮培养的K562细胞相比，共培养的K562细胞在暴露于细胞毒性药物后具有存活优势，但在暴露于As 2 O3后，两组之间的存活率没有差异。As_2O_3与细胞毒药物联合应用的细胞毒作用在悬浮培养组呈相加效应，在共培养组呈协同效应。使用流式细胞术测定发现类似的凋亡反应。As_2O_3处理K562细胞后，K562细胞与BMSCs的粘附能力呈剂量依赖性下降，Western blot分析显示As_2O_3处理K562细胞后，β（1）-整合素表达下调。
The bone marrow microenvironment protects leukemia cells from drug-induced damage, and cell adhesion-mediated drug resistance (CAM-DR) is the main obstacle for the eradication of bone marrow minimal residual disease. In this study, we evaluated the survival response of K562 cells co-cultured with bone marrow stromal cells (BMSCs) derived from patients with chronic myelogenous leukemia (CML). Co-cultured K562 cells had a survival advantage after exposure to cytotoxic drugs compared to suspended K562 cells, but there was no survival difference between the two groups following exposure to As2O3. The cytotoxicity of As2O3 combined with cytotoxic drugs had an additive effect in the suspension group and a synergistic effect in the co-cultured group. Similar apoptotic responses were found using flow cytometry assays. As2O3 treatment caused a dose dependent reduction of the adhesion ability of K562 cells to BMSCs, and Western blot analysis revealed that the treatment of K562 cells with As2O3 led to down-regulation of beta(1)-integrin.