Lee Yueh-Chun, Yu Cheng-Chia, Lan Chih, Lee Che-Hsin, Lee Hsueh-Te, Kuo Yu-Liang, Wang Po-Hui, Chang Wen-Wei
Radiation Oncology Department, Chung Shan Medical University Hospital, Taichung City, Taiwan.
Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
Head Neck. 2016 Apr;38 Suppl 1:E895-904. doi: 10.1002/hed.24124. Epub 2015 Jul 16.
The existence of tumor-initiating cells (TICs) has been described in head and neck cancers. Plasminogen activator inhibitor-1 (PAI-1) has been demonstrated to act as a prognostic factor in head and neck cancers.
Tiplaxtinin (PAI-039), a specific inhibitor of PAI-1, and PAI-1-specific siRNA were used to examine the role of PAI-1 in the self-renewal property of head and neck cancer-TICs by tumorsphere formation. Western blot, real-time polymerase chain reaction, and luciferase-based reporter assay were used to study the effect of PAI-039 in the sex-determining region Y-box 2 (Sox2) expression.
PAI-039 suppressed the self-renewal capability of head and neck cancer-TICs derived from head and neck cancer cell lines through the inhibition of Sox2 expression. PAI-039 decreased the activity of the core promoter and the enhancer of the Sox2 gene in head and neck cancer-TICs. Knockdown of PAI-1 expression also inhibited self-renewal and radioresistance properties of head and neck cancer-TICs.
The inhibition of PAI-1 by PAI-039 or siRNA could suppress head and neck cancer-TICs within head and neck cancer cell lines through the downregulation of Sox2. © 2015 Wiley Periodicals, Inc. Head Neck 38: E895-E904, 2016.
头颈部癌中已证实存在肿瘤起始细胞（TICs）。纤溶酶原激活物抑制剂-1（PAI-1）已被证明可作为头颈部癌的一个预后因素。
使用PAI-1的特异性抑制剂替普拉西丁（PAI-039）和PAI-1特异性小干扰RNA（siRNA），通过肿瘤球形成来检测PAI-1在头颈部癌TICs自我更新特性中的作用。采用蛋白质免疫印迹法、实时聚合酶链反应和基于荧光素酶的报告基因检测法，研究PAI-039对性别决定区Y框2（Sox2）表达的影响。
PAI-039通过抑制Sox2表达，抑制了源自头颈部癌细胞系的头颈部癌TICs的自我更新能力。PAI-039降低了头颈部癌TICs中Sox2基因核心启动子和增强子的活性。敲低PAI-1表达也抑制了头颈部癌TICs的自我更新和放射抗性特性。
PAI-039或siRNA对PAI-1的抑制作用可通过下调Sox2来抑制头颈部癌细胞系中的头颈部癌TICs。©2015威利期刊公司。《头颈》38：E895-E904，2016年。
