Data from Smac Mimetics in Combination with TRAIL Selectively Target Cancer Stem Cells in Nasopharyngeal Carcinoma

作者：Man-Si Wu, Guangfeng Wang, Zhiqiang Zhao, Yi Liang, Heng-bang Wang, Miao-yi Wu, Ping Min, Lizhen Chen, Qi‐Sheng Feng, Jin-xin Bei, Yi‐Xin Zeng, Dajun Yang · 年份：2023 · DOI：10.1158/1535-7163.c.6536235 · 研究领域：Cell death mechanisms and regulation、MicroRNA in disease regulation、RNA Interference and Gene Delivery

<div>AbstractNasopharyngeal carcinoma is a common malignancy in Southern China. After radiotherapy and chemotherapy, a considerable proportion of patients with nasopharyngeal carcinoma suffered tumor relapse and metastasis. Cancer stem cells (CSC) have been shown with resistance against therapies and thus considered as the initiator of recurrence and metastasis in tumors, where the antiapoptotic property of CSCs play an important role. Smac/DIABLO is an inverse regulator for the inhibitors of apoptosis protein family (IAP), which have been involved in apoptosis. Here, the effects of Smac mimetics on the CSCs of nasopharyngeal carcinoma were studied both in vitro and in vivo, using two clones of nasopharyngeal carcinoma cell line CNE2 as models. We found that one of the clones, S18, had CSC-like properties and IAPs were overexpressed. The combination of Smac mimetics and TNF-related apoptosis-inducing ligand (TRAIL) can reduce the percentage of SP cells and inhibit the colony- and sphere-forming abilities of S18 cells, indicating their ability to attenuate the CSCs. Moreover, in a nasopharyngeal carcinoma xenograft model, the administration of Smac mimetics in combination with TRAIL also led to the elimination of nasopharyngeal carcinoma stem cells. Furthermore, the Smac mimetics in combination with TRAIL induced the degradation of cIAP1 and XIAP and thus induced apoptosis in vitro and in vivo<...