Wang Fei, Sheng Jian-Fei, Cai Lei, Xu Yong, Liao Hua, Tao Ze-Zhang
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.
ORL J Otorhinolaryngol Relat Spec. 2018;80(5-6):227-237. doi: 10.1159/000489461. Epub 2018 Sep 13.
To investigate the possible telomerase and alternative lengthening of telomeres (ALT) mechanisms influencing the apoptosis of laryngeal squamous cells.
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.
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.
The inhibition of telomere-related genes inhibited the growth of laryngeal squamous cell carcinoma by promoting cell apoptosis via the PI3K/Akt pathway.
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。
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。
沉默ALT和端粒酶机制相关基因后，Bax和Bcl-2增加，核因子（NF）-κB易位和PI3K/Akt磷酸化受到抑制。
抑制端粒相关基因通过PI3K/Akt途径促进细胞凋亡，从而抑制喉鳞状细胞癌的生长。
