Proteomic analysis of docetaxel resistance in human nasopharyngeal carcinoma cells using the two-dimensional gel electrophoresis method
Proteomic analysis of docetaxel resistance in human nasopharyngeal carcinoma cells using the two-dimensional gel electrophoresis method
复制标题
采用二维凝胶电泳法对人鼻咽癌细胞多西紫杉醇耐药性进行蛋白质组学分析。
DOI：
10.1097/cad.0000000000000388
复制
发表时间：
2016-09-01
影响因子：
2.3
通讯作者：
Hu, XiaoLin
中科院分区：
文献类型：
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作者：
Peng, Xingchen;Gong, Fengming M.;Hu, XiaoLin
多西他赛为基础的化疗已被推荐用于晚期鼻咽癌（NPC）。然而，由于获得性耐药性，治疗失败经常发生。本研究采用递增剂量多西他赛治疗鼻咽癌6个月以上，建立了鼻咽癌耐药细胞系CNE-2 R。应用双向电泳和电喷雾质谱技术（ESI-Q-TOF-MS）比较人鼻咽癌CNE-2细胞和鼻咽癌耐药CNE-2 R细胞中耐药相关蛋白的差异表达。结果，鉴定出24个差异表达蛋白，包括11个表达增加的蛋白和13个表达减少的蛋白。这些蛋白质在代谢、信号转导、钙离子结合、免疫应答、蛋白水解等多种生物学过程中发挥作用，其中α-烯醇化酶（ENO 1）在CNE-2 R中表达显著上调。通过shRNA抑制ENO 1恢复CNE-2 R细胞对多西他赛的敏感性。此外，ENO 1的过表达可促进CNE-2细胞对多西他赛的获得性耐药。Western blot和逆转录PCR检测结果证实，α-烯醇化酶在耐药鼻咽癌组织中表达上调。发现这样的蛋白质可能会改善导致多西他赛耐药的分子机制的解释。版权所有（C）2016威科医疗集团All rights reserved.
Docetaxel-based chemotherapy has been recommended for advanced nasopharyngeal carcinoma (NPC). However, treatment failure often occurs because of acquired drug resistance. In this study, a docetaxel-resistant NPC cell line CNE-2R was established with increasing doses of docetaxel for more than 6 months. Two-dimensional gel electrophoresis and ESI-Q-TOF-MS were used to compare the differential expression of docetaxel-resistance-associated proteins between human NPC CNE-2 cells and docetaxel-resistant CNE-2R cells. As a result, 24 differentially expressed proteins were identified, including 11 proteins with increased expression and 13 proteins with decreased expression. These proteins function in diverse biological processes such as metabolism, signal transduction, calcium ion binding, immune response, proteolysis, and so on. Among these, a-enolase (ENO1), significantly upregulated in CNE-2R, was selected for detailed analysis. Inhibition of ENO1 by shRNA restored CNE-2R cells' sensitivity to docetaxel. Moreover, overexpression of ENO1 could facilitate the development of acquired resistance of docetaxel in CNE-2 cells. Western blot and reverse-transcription PCR data of clinical samples confirmed that alpha-enolase was upregulated in docetaxel-resistant human NPC tissues. Finding such proteins might improve interpretation of the molecular mechanisms leading to the acquisition of docetaxel chemoresistance. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.