Epithelial-mesenchymal transition is necessary for acquired resistance to cisplatin and increases the metastatic potential of nasopharyngeal carcinoma cells.
Epithelial-mesenchymal transition is necessary for acquired resistance to cisplatin and increases the metastatic potential of nasopharyngeal carcinoma cells.
复制标题
DOI：
10.3892/ijmm.2013.1538
复制
发表时间：
2014
影响因子：
5.4
通讯作者：
Pei Zhang;Hao Liu;F. Xia;Q. Zhang;Y. Zhang;Qing-Chun Zhao;Zhenhua Chao;Zhi-wen Jiang;C. Jian
中科院分区：
文献类型：
--
作者：
Pei Zhang;Hao Liu;F. Xia;Q. Zhang;Y. Zhang;Qing-Chun Zhao;Zhenhua Chao;Zhi-wen Jiang;C. Jian
放疗和辅助顺铂（DDP）化疗是治疗鼻咽癌（NPC）的标准方法。然而，最近化疗耐药变得越来越普遍，导致这种联合疗法治疗鼻咽癌的失败。本研究的目的是评估 DDP 耐药性 NPC 细胞的细胞形态、运动性和分子变化与上皮间质转化 (EMT) 的关系。 CNE2细胞持续暴露于增加剂量的DDP，以建立稳定的DDP抗性细胞系（CNE2/DDP细胞）。人类 NPC 细胞系 HNE1、CNE2、HNE1/DDP 和 CNE2/DDP 用于检查化疗耐药性与癌细胞获得 EMT 样表型之间的关联。 DDP 抗性细胞对 DDP 处理的敏感性低于 HNE1 细胞，细胞活力测定、蛋白质印迹分析和 qRT-PCR 显示已获得化学抗性。通过伤口愈合和 Transwell Boyden 室测定检查的 HNE1/DDP 细胞表现出增加的迁移和侵袭潜力。通过蛋白质印迹分析和 qRT-PCR 观察到，DDP 抗性细胞表现出与 EMT 一致的形态和分子变化。这些变化包括形状变得更像纺锤体、极性丧失和伪足形成、E-钙粘蛋白和β-连环蛋白下调以及波形蛋白、纤连蛋白和基质金属蛋白酶 (MMP)-9 上调。此外，EMT 相关转录因子 Snail、Slug、Twist 和锌指 E 盒结合同源框 1 (ZEB1) 的水平在 DDP 耐药的 NPC 细胞中较高。这些数据表明，NPC 细胞 DDP 抗性的发展伴随着可诱导的 EMT 样变化，且体外转移潜力增加。进一步阐明 DDP 耐药性和 EMT 之间的关联可能有助于未来开发治疗化疗耐药肿瘤的新治疗方法。
Radiotherapy and adjuvant cisplatin (DDP) chemotherapy are standard approaches used in the treatment of nasopharyngeal carcinoma (NPC). However, resistance to chemotherapy has recently become more common, resulting in the failure of this combination therapy for NPC. The aim of the present study was to assess the cellular morphology, motility and molecular changes in DDP-resistant NPC cells in relation to epithelial-mesenchymal transition (EMT). CNE2 cells were continuously exposed to increasing doses of DDP to establish a stable cell line resistant to DDP (CNE2/DDP cells). The human NPC cell lines, HNE1, CNE2, HNE1/DDP and CNE2/DDP, were used to examine the association between chemoresistance and the acquisition of an EMT-like phenotype of cancer cells. The DDP-resistant cells were less sensitive than the HNE1 cells to treatment with DDP, and were shown by a cell viability assay, western blot analysis and qRT-PCR to have acquired chemoresistance. The HNE1/DDP cells examined by wound healing and Transwell Boyden chamber assays exhibited an increased migration and invasion potential. The DDP-resistant cells exhibited morphological and molecular changes consistent with EMT, as observed by western blot analysis and qRT-PCR. These changes included becoming more spindle-like in shape, a loss of polarity and formation of pseudopodia, the downregulation of E-cadherin and β-catenin and the upregulation of vimentin, fibronectin and matrix metalloproteinase (MMP)-9. Moreover, the levels of the EMT-related transcription factors, Snail, Slug, Twist and zinc finger E-box binding homeobox 1 (ZEB1), were higher in the DDP‑resistant NPC cells. These data suggest that the development of DDP resistance of NPC cells is accompanied by inducible EMT-like changes with an increased metastatic potential in vitro. Further elucidation of the association between resistance to DDP and EMT may facilitate the future development of novel therapeutic approaches for the treatment of chemoresistant tumors.