NOTCH1 inhibition enhances the efficacy of conventional chemotherapeutic agents by targeting head neck cancer stem cell

作者：Zhili Zhao, Lu Zhang, Cong‐Fa Huang, Si‐Rui Ma, Lin‐Lin Bu, Jianfeng Liu, Guang‐Tao Yu, Bing Liu, J. Silvio Gutkind, Ashok B. Kulkarni, Wen‐Feng Zhang, Zhi‐Jun Sun · 发表于：Scientific Reports · 年份：2016 · DOI：10.1038/srep24704 · 被引用次数：97 · 研究领域：Cancer Cells and Metastasis、Epigenetics and DNA Methylation、Developmental Biology and Gene Regulation

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 ability in vitro and in 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.