端粒酶与端粒替代延长机制通过PI3K/Akt信号通路调控喉癌细胞凋亡。

The Telomerase and Alternative Lengthening of Telomeres Mechanisms Regulate Laryngeal Cancer Cell Apoptosis via the PI3K/Akt Pathway.

作者信息

Wang Fei, Sheng Jian-Fei, Cai Lei, Xu Yong, Liao Hua, Tao Ze-Zhang

机构信息

Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, China.

Department of Otolaryngology-Head and Neck Surgery, Maternal and Child Health Hospital of Hubei Province, Wuhan, China.

出版信息

ORL J Otorhinolaryngol Relat Spec. 2018;80(5-6):227-237. doi: 10.1159/000489461. Epub 2018 Sep 13.

DOI:10.1159/000489461

PMID:30212832

Abstract

PURPOSE

To investigate the possible telomerase and alternative lengthening of telomeres (ALT) mechanisms influencing the apoptosis of laryngeal squamous cells.

MATERIALS AND METHODS

The effects of the telomerase mechanism were observed by knockdown of human telomerase reverse transcriptase (hTERT). The ALT mechanism was induced by silencing related genes including TRF2, RAD51, and NBS1. Effects of telomerase and ALT mechanisms on tumor development were confirmed by xenograft tumors model. Tumor cell apoptosis was investigated by flow cytometry and Hoechst staining. Caspase-3 activity assay and Western blot were performed to investigate the possible mechanisms.

RESULTS

After silencing ALT- and telomerase mechanism-related genes, Bax and Bcl-2 were increased, and nuclear factor (NF)-κB translocation and PI3K/Akt phosphorylation were inhibited.

CONCLUSIONS

The inhibition of telomere-related genes inhibited the growth of laryngeal squamous cell carcinoma by promoting cell apoptosis via the PI3K/Akt pathway.

摘要

目的

研究可能影响喉鳞状细胞凋亡的端粒酶和端粒替代延长（ALT）机制。

材料与方法

通过敲低人端粒酶逆转录酶（hTERT）观察端粒酶机制的作用。通过沉默包括TRF2、RAD51和NBS1在内的相关基因诱导ALT机制。通过异种移植肿瘤模型证实端粒酶和ALT机制对肿瘤发展的影响。通过流式细胞术和Hoechst染色研究肿瘤细胞凋亡。进行Caspase-3活性测定和蛋白质印迹以研究可能的机制。