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体外和体内抑制自噬使 clioquinol 联合锌增敏鼻咽癌细胞干细胞样细胞

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

机构信息

Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China.

Hubei Key Laboratory of Tumor Biological Behaviors, Wuhan, China; Hubei Cancer Clinical Study Center, Zhongnan Hospital of Wuhan University, Wuhan, China.

出版信息

Int J Biol Sci. 2020 Jan 14;16(5):777-789. doi: 10.7150/ijbs.40305. eCollection 2020.

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 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 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.

摘要

鼻咽癌(NPC)放疗后局部区域复发是治疗失败的主要类型之一。本研究旨在探讨 NPC 患者场内复发的可能原因,以期开发有效的治疗方法。我们的研究表明,复发 NPC 患者肿瘤组织中的 CD44 和自噬蛋白高于无复发患者。实验进一步证实,具有增强自噬活性的癌症干细胞(CSC)对辐射具有更强的抵抗力。用氯喹(CQ)联合锌处理可通过抑制自噬、激活半胱天冬酶系统和损害 DNA 损伤修复,明显提高 CNE-2s 细胞的放射敏感性。实验进一步证实了我们的发现。我们的结果表明,CSC 和增强的自噬活性可能参与 NPC 的场内复发,CQ 联合锌可能是治疗 NPC 复发的重要方法。

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