Identification of up- and down-regulated proteins in doxorubicin-resistant uterine cancer cells: Reticulocalbin-1 plays a key role in the development of doxorubicin-associated resistance
Identification of up- and down-regulated proteins in doxorubicin-resistant uterine cancer cells: Reticulocalbin-1 plays a key role in the development of doxorubicin-associated resistance
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DOI：
10.1016/j.phrs.2014.08.007
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发表时间：
2014-12-01
影响因子：
9.3
通讯作者：
Chan, Hong-Lin
中科院分区：
文献类型：
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作者：
May, Eugenie Wong Soon;Lin, Szu-Ting;Chan, Hong-Lin
耐药性是癌症化疗治疗失败的常见原因。在这项研究中，一对子宫肉瘤癌细胞系，MES-SA，和阿霉素耐药的合作伙伴，MES-SA/DxR-2 μ M细胞和MES-SA/DxR-8 μ M细胞，作为一个模型系统，研究耐药依赖性蛋白质组的改变，并确定潜在的治疗靶点。我们使用二维差异凝胶电泳（2D-DIGE）和基质辅助激光解吸电离飞行时间质谱（MALDI-TOF MS）进行这项研究，结果显示，阿霉素耐药改变了208个蛋白质的表达，其中129个鉴定的蛋白质表现出剂量依赖性的方式响应于耐药水平。进一步的研究使用RNA干扰、H2A.X磷酸化测定、细胞活力分析以及针对网织红蛋白-1（RCN 1）蛋白的细胞凋亡分析来证明其对阿霉素耐药性形成以及减弱阿霉素相关DNA双链断裂的效力。综上所述，我们的研究结果提供了有用的诊断标志物和治疗候选人，如RCN 1用于治疗阿霉素耐药的子宫癌。(C)2014爱思唯尔有限公司版权所有。
Drug resistance is a frequent cause of failure in cancer chemotherapy treatments. In this study, a pair of uterine sarcoma cancer lines, MES-SA, and doxorubicin-resistant partners, MES-SA/DxR-2 mu M cells and MES-SA/DxR-8 mu M cells, as a model system to investigate resistance-dependent proteome alterations and to identify potential therapeutic targets. We used two-dimensional differential gel electrophoresis (2D-DIGE) and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) to perform this research and the results revealed that doxorubian-resistance altered the expression of 208 proteins in which 129 identified proteins showed dose-dependent manners in response to the levels of resistance. Further studies have used RNA interference, H2A.X phosphorylation assay, cell viability analysis, and analysis of apoptosis against reticulocalbin-1 (RCN1) proteins, to prove its potency on the formation of doxorubicin resistance as well as the attenuation of doxorubicin-associated DNA double strand breakage. To sum up, our results provide useful diagnostic markers and therapeutic candidates such as RCN1 for the treatment of doxorubicin-resistant uterine cancer. (C) 2014 Elsevier Ltd. All rights reserved.