Downregulation of cancer stem cell properties via mTOR signaling pathway inhibition by rapamycin in nasopharyngeal carcinoma

Yang,Chunguang; Zhang,Yue; Zhang,Yu; Zhang,Ziheng; Peng,Jianhua; Li,Zhi; Han,Liang; You,Quanjie; Chen,Xiaoyu; Rao,Xingwang; Zhu,Yi; Liao,Zhisu

doi:10.3892/ijo.2015.3100

Downregulation of cancer stem cell properties via mTOR signaling pathway inhibition by rapamycin in nasopharyngeal carcinoma

Authors:
- Chunguang Yang
- Yue Zhang
- Yu Zhang
- Ziheng Zhang
- Jianhua Peng
- Zhi Li
- Liang Han
- Quanjie You
- Xiaoyu Chen
- Xingwang Rao
- Yi Zhu
- Zhisu Liao
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Affiliations: Department of Otolaryngology, Head and Neck Surgery, Xiang Ya Hospital, Central South University, Changsha, Hunan, P.R. China, Department of Otolaryngology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, P.R. China, Department of Otolaryngology, Dong Feng Hospital, Hubei University of Medicine, Shiyan, Hubei, P.R. China
Published online on: July 21, 2015 https://doi.org/10.3892/ijo.2015.3100
Pages: 909-917
Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Rapamycin, a mammalian target of rapamycin (mTOR) signaling inhibitor, inhibits cancer cell proliferation and tumor formation, including in nasopharyngeal carcinoma (NPC), which we proved in a previous study. However, whether rapamycin affects cancer stem cells (CSCs) is unclear. In examining samples of NPCs, we found regions of CD44-positive cancer cells co-expressing the stem cell biomarker OCT4, suggesting the presence of CSCs. Following this, we used double-label immunohistochemistry to identify whether the mTOR signaling pathway was activated in CD44-positive CSCs in NPCs. We used a CCK-8 assay and western blotting to explore whether the stem cell biomarkers CD44 and SOX2 and the invasion protein MMP-2 could be suppressed by treatment with rapamycin in cultured primary NPC cells and secondary tumors in BALB/c nude mice. Interestingly, we found that rapamycin inhibited mTOR signaling in addition to simultaneously downregulating the expression of CD44, SOX2 and MMP-2 and that it affected cell growth and tumor size and weight both in vitro and in vivo. Collectively, we confirmed for the first time that CSC properties are reduced and invasion potential is restrained in response to mTOR signaling inhibition in NPC. This evidence indicates that the targeted inhibition of CSC properties may provide a novel strategy to treat cancer.

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