当前位置: X-MOL 学术J. Genet. Genomics › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Suppressed mitochondrial respiration via NOX5-mediated redox imbalance contributes to the antitumor activity of anlotinib in oral squamous cell carcinoma
Journal of Genetics and Genomics ( IF 6.6 ) Pub Date : 2021-07-15 , DOI: 10.1016/j.jgg.2021.06.014
Zhexun Huang 1 , Qiao Su 2 , Wuguo Li 2 , Hui Ren 1 , Huiqiang Huang 3 , Anxun Wang 1
Affiliation  

Anlotinib, a novel multitarget tyrosine kinase inhibitor, has shown promising results in the management of various carcinomas. This study aimed to investigate the antitumor activity of anlotinib in oral squamous cell carcinoma (OSCC) and the underlying molecular mechanism. A retrospective clinical study revealed that anlotinib improved the median progression-free survival (mPFS) and median overall survival (mOS) of patients with recurrent and metastatic (R/M) OSCC, respectively. Functional studies revealed that anlotinib markedly inhibited in vitro proliferation of OSCC cells and impeded in vivo tumor growth of OSCC patient-derived xenograft models. Mechanistically, RNA-sequencing identified that oxidative stress, oxidative phosphorylation and AKT/mTOR signaling were involved in anlotinib-treated OSCC cells. Anlotinib upregulated NADPH oxidase 5 (NOX5) expression, elevated reactive oxygen species (ROS) production, impaired mitochondrial respiration, and promoted apoptosis. Moreover, anlotinb also inhibited phospho-Akt (p-AKT) expression and elevated p-eIF2α expression in OSCC cells. NOX5 knockdown attenuated these inhibitory effects and cytotoxicity in anlotinib-treated OSCC cells. Collectively, we demonstrated that anlotinib monotherapy demonstrated favorable anticancer activity and manageable toxicities in patients with R/M OSCC. The antitumor activity of anlotinib in OSCC may be mainly involved in the suppression of mitochondrial respiration via NOX5-mediated redox imbalance and the AKT/eIF2α pathway.



中文翻译:


通过 NOX5 介导的氧化还原失衡抑制线粒体呼吸有助于安罗替尼在口腔鳞状细胞癌中的抗肿瘤活性



安罗替尼是一种新型多靶点酪氨酸激酶抑制剂,在多种癌症的治疗中显示出良好的效果。本研究旨在探讨安罗替尼在口腔鳞状细胞癌(OSCC)中的抗肿瘤活性及其潜在分子机制。一项回顾性临床研究显示,安罗替尼分别改善了复发性和转移性 (R/M) OSCC 患者的中位无进展生存期 (mPFS) 和中位总生存期 (mOS)。功能研究表明,安罗替尼显着抑制 OSCC 细胞的体外增殖,并阻止 OSCC 患者异种移植模型的体内肿瘤生长。从机制上讲,RNA 测序发现氧化应激、氧化磷酸化和 AKT/mTOR 信号传导参与了安罗替尼治疗的 OSCC 细胞。安罗替尼上调 NADPH 氧化酶 5 ( NOX5 ) 表达,增加活性氧 (ROS) 产生,损害线粒体呼吸并促进细胞凋亡。此外,anlotinb 还抑制 OSCC 细胞中的磷酸Akt (p-AKT) 表达并升高p-eIF2α表达。 NOX5敲低减弱了安罗替尼处理的 OSCC 细胞中的这些抑制作用和细胞毒性。总的来说,我们证明安罗替尼单一疗法在 R/M OSCC 患者中表现出良好的抗癌活性和可控制的毒性。安罗替尼在 OSCC 中的抗肿瘤活性可能主要通过 NOX5 介导的氧化还原失衡和 AKT/eIF2α 途径抑制线粒体呼吸。

更新日期:2021-09-17
down
wechat
bug