%0 Journal Article %A MASAKATSU FUKUDA %A YUDAI OGASAWARA %A HIROYASU HAYASHI %A AYAKO OKUYAMA %A JUNYA SHIONO %A KATSUYUKI INOUE %A HIDEAKI SAKASHITA %T Down-regulation of Glutathione Peroxidase 4 in Oral Cancer Inhibits Tumor Growth Through SREBP1 Signaling %D 2021 %R 10.21873/anticanres.14944 %J Anticancer Research %P 1785-1792 %V 41 %N 4 %X 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. Materials and Methods: Quantitative RT-PCR and immunoblot analysis were carried out. Cell viability assay, apoptosis detection assay, immunohistochemistry and GPX4 knockdown were performed. Results: 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. Conclusion: GPX4 appears to play an important role in oral cancer proliferation. %U https://ar.iiarjournals.org/content/anticanres/41/4/1785.full.pdf