Hyperthermia inhibits growth of nasopharyngeal carcinoma through degradation of c-Myc

International Journal of Hyperthermia

Lei Wang¹  Xinqiang Li¹  Shichao Duan¹  Wencai Li¹  Yingjuan Zheng²  Yongqiang Yang²  Daoke Yang³  Xiaole Li³  Rick F. Thorne⁴  Qing Zhang⁴ 

[1] Department of Pathology, First Affiliated Hospital of Zhengzhou University;Department of Radiotherapy, First Affiliated Hospital of Zhengzhou University;School of Basic Medical Sciences, Zhengzhou University;Translational Research Institute, Henan Provincial People’s Hospital, Academy of Medical Science, Zhengzhou University;

关键词: c-myc;    hyperthermia;    heat shock;    nasopharyngeal carcinoma;    ubiquitination;   

DOI  :  10.1080/02656736.2022.2038282

来源: DOAJ

【 摘 要 】

Background Hyperthermia is a widely used adjunct treatment for different cancers including nasopharyngeal carcinoma (NPC). The protooncogene c-Myc is up-regulated in NPC and its expression is associated with poor prognosis. Objective We hypothesized that c-Myc constitutes an important hyperthermia treatment target, and we investigated its contribution to hyperthermia responses in NPC. Methods The growth of the human NPC cell lines CNE1 and CNE2 was analyzed using CCK-8 and clonogenicity assays after 43 °C hyperthermia, knockdown or overexpression of c-Myc. Flow cytometry measurements assessed cell cycle parameters and apoptosis, while levels of c-Myc together with key transcriptional targets were determined using qPCR and Western blotting. Parallel experiments were undertaken using NPC xenografts in nude mice and lastly, global transcriptomic changes were determined using ‘RNAseq’. Results Hyperthermia increased the ubiquitination and proteasomal destruction of c-Myc, causing a rapid decline in c-Myc protein levels in NPC cells. Similar to c-Myc knockdown, NPC cells treated with hyperthermia showed growth inhibition associated with the downregulation of c-Myc target genes. Moreover, low levels of c-Myc could be sustainably repressed in NPC cells through repeated hyperthermia treatments. Importantly, the key findings of growth inhibition and decreased c-Myc protein levels were reproduced in NPC tumor xenografts. Bioinformatic analyses showed that downregulation of c-Myc constituted a central node in the hyperthermia response of NPC cells. Conclusion Our study reveals that hyperthermia can readily destabilize c-Myc levels in NPC cells and inhibit tumor growth. This proposes new strategies for implementing hyperthermia to target c-Myc-driven cancers to improve therapeutic efficacy.

【 授权许可】

Unknown