Int J Biol Sci 2020; 16(5):777-789. doi:10.7150/ijbs.40305

Research Paper

Radiosensitization of Clioquinol Combined with Zinc in the Nasopharyngeal Cancer Stem-like Cells by Inhibiting Autophagy in Vitro and in Vivo

Yuan Ke1,2*, Chaoyan Wu3*, Yifei Zeng1,2, Mengge Chen1,2, Yonghong Li1,2, Conghua Xie1,2, Yunfeng Zhou1,2, Yahua Zhong1,2, Haijun Yu1,2✉

1. Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China
2. Hubei Key Laboratory of Tumor Biological Behaviors, Wuhan, China; Hubei Cancer Clinical Study Center, Zhongnan Hospital of Wuhan University, Wuhan, China
3. Department of Integrated Traditional Chinese Medicine and Western medicine, Zhongnan Hospital of Wuhan University, Wuhan, China
* These authors contributed equally to this work.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Citation:
Ke Y, Wu C, Zeng Y, Chen M, Li Y, Xie C, Zhou Y, Zhong Y, Yu H. Radiosensitization of Clioquinol Combined with Zinc in the Nasopharyngeal Cancer Stem-like Cells by Inhibiting Autophagy in Vitro and in Vivo. Int J Biol Sci 2020; 16(5):777-789. doi:10.7150/ijbs.40305. Available from http://www.ijbs.com/v16p0777.htm

File import instruction

Abstract

Loco-regional recurrence of nasopharyngeal carcinoma (NPC) after radiation therapy is one of the main types of treatment failure. This study is aimed to explore the possible causes of inside-field recurrence of NPC patients in order to develop effective treatment methods. Our study indicated that CD44 and autophagy proteins in tumor tissues of patients with recurrent NPC are higher than that of the relapse free patients. The in vitro experiments further confirmed that cancer stem cells (CSCs) were more radioresistant with enhanced autophagy activity. Treatment with clioquinol (CQ) combined with zinc could obviously enhance the radiosensitivity of CNE-2s cells through autophagy inhibition, activation of the caspase system and impairment of DNA damage repair. The in vivo experiments have further consolidated our findings. Our results suggest that CSCs and enhanced autophagy activity may be involved in the inside-field recurrence of NPC, and CQ combined with zinc could be an important therapeutic approach for recurrent NPC.