关键词: 铁死亡, 口腔鳞癌, 脂质过氧化

Abstract: AIM : To explore whether the stearoyl-CoA desaturase-1 (SCD1) inhibitor CAY-10566 can induce ferroptosis in oral squamous cell carcinoma (OSCC) cells, enhance their sensitivity to cisplatin, and preliminarily investigate the relevant molecular mechanisms. METHODS:The expression level of SCD1 in OSCC tissues was evaluated through bioinformatics analysis and collection of clinical specimens; cell viability was detected using the CCK-8 assay; the levels of reactive oxygen species (ROS) and lipid ROS were measured by flow cytometry; the levels of malondialdehyde (MDA) and reduced glutathione (GSH) were determined with MDA detection kit and GSH detection kit, respectively; and the protein expression levels of GPX4, mTOR, SREBP1, SCD1, and HMOX1 were detected by Western blot. RESULTS: SCD1 showed significantly high expression in OSCC tissues. After combined treatment with CAY-10566 and cisplatin, the viability of OSCC cells was significantly reduced, the level of lipid peroxidation was increased, and the expression of GPX4 was inhibited; this effect could be reversed by the ferroptosis inhibitor Fer-1. In addition, CAY-10566 could upregulate the expression of HMOX1 in OSCC cells and inhibit the expression of mTOR, mSREBP1, and SCD1 proteins. CONCLUSION: CAY-10566 can induce ferroptosis in OSCC cells and enhance their sensitivity to cisplatin, and its mechanism of action may be related to the upregulation of HMOX1 and the inhibition of the mTOR/SREBP1/SCD1 axis.

Key words: oral squamous cell carcinoma, lipid peroxidation, ferroptosis