Fukuda Masakatsu, Ogasawara Yudai, Hayashi Hiroyasu, Okuyama Ayako, Shiono Junya, Inoue Katsuyuki, Sakashita Hideaki
Division of Oral and Maxillofacial Surgery, Department of Diagnostic and Therapeutic Sciences, Meikai University School of Dentistry, Saitama, Japan
Division of Oral and Maxillofacial Surgery, Department of Diagnostic and Therapeutic Sciences, Meikai University School of Dentistry, Saitama, Japan.
Anticancer Res. 2021 Apr;41(4):1785-1792. doi: 10.21873/anticanres.14944.
BACKGROUND/AIM: This study aimed to elucidate the role of glutathione peroxidase 4 (GPX4) on the sterol regulatory element binding proteins (SREBPs)-proliferation pathway in oral cancer cells, and determine its protein expression in oral cancer tissues.
Quantitative RT-PCR and immunoblot analysis were carried out. Cell viability assay, apoptosis detection assay, immunohistochemistry and GPX4 knockdown were performed.
The levels of both GPX4 mRNA and protein were highest in SAS cells. GPX4 knockdown in SAS cells, a human oral squamous cell carcinoma cell line, using GPX4 siRNA resulted in a reduction in cell number, which appeared to be due to non-apoptotic cell death such as ferroptosis. Furthermore, SREBP was clearly down-regulated by GPX4 knockdown in SAS cells. Immunopositivity for GPX4 was revealed on the membrane of human oral squamous cell carcinoma cells, and this was correlated with p53 immunoreactivity.
GPX4 appears to play an important role in oral cancer proliferation.
背景/目的：本研究旨在阐明谷胱甘肽过氧化物酶4（GPX4）在口腔癌细胞中固醇调节元件结合蛋白（SREBPs）-增殖途径中的作用，并确定其在口腔癌组织中的蛋白表达。
进行了定量逆转录聚合酶链反应（qRT-PCR）和免疫印迹分析。开展了细胞活力测定、凋亡检测试验、免疫组织化学和GPX4基因敲低实验。
GPX4的信使核糖核酸（mRNA）和蛋白水平在SAS细胞中最高。使用GPX4小干扰RNA（siRNA）敲低人口腔鳞状细胞癌细胞系SAS细胞中的GPX4，导致细胞数量减少，这似乎是由于铁死亡等非凋亡性细胞死亡所致。此外，在SAS细胞中，GPX4基因敲低明显下调了SREBP。在人口腔鳞状细胞癌细胞膜上显示出GPX4免疫阳性，且这与p53免疫反应性相关。
GPX4似乎在口腔癌增殖中发挥重要作用。
