机构：[a]Department of Stomatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou,[b]Center of Stomatology, The second affiliated hospital of Soochow University, Suzhou, China
Background/Aims: mTOR is an important therapeutic target for human head and neck squamous cell carcinoma (HNSCC). The current study tested the anti-HNSCC cell activity by a mTOR kinase inhibitor CZ415. Methods: HNSCC cells were treated with CZ415. Cell death was tested by lactate dehydrogenase (LDH) assay and MTT assay. Cell proliferation was tested by BrdU ELISA assay and [H-3] thymidine incorporation assay, with apoptosis assayed by the TUNEL staining. A Western blotting assay was applied to test autophagy-associated proteins, mTOR and signalings. The nude mice xenograft model was established to study CZ415-mediated anti-tumor activity. Results: In established (SCC-9, SQ20B and A253 lines) and primary human HNSCC cells, CZ415 efficiently inhibited cell survival and proliferation. CZ415 blocked mTORC1/2 activation and inhibited ERK in HNSCC cells. CZ415 provoked feedback autophagy activation. Conversely, autophagy inhibitors (3-methyladenine and chloroquine) or Beclin-1 shRNA sensitized CZ415-induced HNSCC cell death. In vivo, CZ415 gavage inhibited SCC9 tumor growth in nude mice, showing higher efficiency against Beclin-1-silenced tumors. Conclusion: CZ415 inhibits HNSCC cell growth in vitro and in vivo. Inhibition of autophagy can further sensitize CZ415 against HNSCC cells. (C) 2018 The Author(s) Published by S. Karger AG, Basel.y
基金：
This work was generously supported by grants from the Wenzhou Science and Technology Bureau (Y20130260).
第一作者机构：[a]Department of Stomatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou,[*1]Department of Stomatology, The First Affiliated Hospital of Wenzhou Medical University, Nanbaixiang, Ouhai, Wenzhou, ZheJiang Province (China)
通讯作者：
通讯机构：[*1]Department of Stomatology, The First Affiliated Hospital of Wenzhou Medical University, Nanbaixiang, Ouhai, Wenzhou, ZheJiang Province (China)
推荐引用方式(GB/T 7714)：
Jing Xie,Quan Li,Xi Ding,et al.Targeting mTOR by CZ415 Inhibits Head and Neck Squamous Cell Carcinoma Cells[J].CELLULAR PHYSIOLOGY AND BIOCHEMISTRY.2018,46(2):676-686.doi:10.1159/000488724.
APA：
Jing Xie,Quan Li,Xi Ding&Yunyun Gao.(2018).Targeting mTOR by CZ415 Inhibits Head and Neck Squamous Cell Carcinoma Cells.CELLULAR PHYSIOLOGY AND BIOCHEMISTRY,46,(2)
MLA：
Jing Xie,et al."Targeting mTOR by CZ415 Inhibits Head and Neck Squamous Cell Carcinoma Cells".CELLULAR PHYSIOLOGY AND BIOCHEMISTRY 46..2(2018):676-686
