NOTCH1 inhibition enhances the efficacy of conventional chemotherapeutic agents by targeting head neck cancer stem cell.
NOTCH1 inhibition enhances the efficacy of conventional chemotherapeutic agents by targeting head neck cancer stem cell.
复制标题
NOTCH1抑制通过靶向头颈癌干细胞增强传统化疗药物的疗效
DOI：
10.1038/srep24704
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发表时间：
2016-04-25
影响因子：
4.6
通讯作者：
Sun ZJ
中科院分区：
文献类型：
--
作者：
Zhao ZL;Zhang L;Huang CF;Ma SR;Bu LL;Liu JF;Yu GT;Liu B;Gutkind JS;Kulkarni AB;Zhang WF;Sun ZJ
癌症干细胞（CSC）被认为是肿瘤发生和化学抗性的原因。本研究旨在探讨抑制NOTCH 1通路靶向治疗头颈部鳞状细胞癌（HNSCC）的可能性，并探讨抑制NOTCH 1通路与常规化疗联合应用的协同效应。NOTCH 1/HES 1在人HNSCC中表达升高，尤其是在化疗后和淋巴结转移的组织中，且与肿瘤干细胞标志物相关。NOTCH 1抑制剂DAPT（GSI-IX）在体外和体内显著降低CSCs数量和肿瘤自我更新能力。流式细胞术分析显示，N 0 TCH 1抑制单独或与化疗剂（即顺铂、多西他赛和5-氟尿嘧啶）组合降低CSC频率。NOTCH 1阻断和化疗的组合策略协同地减弱化疗富集的CSC群体，有望在未来的临床试验中进行潜在的治疗开发。
Cancer stem cells (CSCs) are considered responsible for tumor initiation and chemoresistance. This study was aimed to investigate the possibility of targeting head neck squamous cell carcinoma (HNSCC) by NOTCH1 pathway inhibition and explore the synergistic effect of combining NOTCH inhibition with conventional chemotherapy. NOTCH1/HES1 elevation was found in human HNSCC, especially in tissue post chemotherapy and lymph node metastasis, which is correlated with CSCs markers. NOTCH1 inhibitor DAPT (GSI-IX) significantly reduces CSCs population and tumor self-renewal abilityin vitroandin vivo. Flow cytometry analysis showed that NOTCH1 inhibition reduces CSCs frequency either alone or in combination with chemotherapeutic agents, namely, cisplatin, docetaxel, and 5-fluorouracil. The combined strategy of NOTCH1 blockade and chemotherapy synergistically attenuated chemotherapy-enriched CSC population, promising a potential therapeutic exploitation in future clinical trial.