中国临床药理学与治疗学2025，Vol.30Issue(8)：1009-1016,8.DOI:10.12092/j.issn.1009-2501.2025.08.001
SCD1抑制剂CAY-10566通过诱导口腔鳞癌细胞铁死亡增敏顺铂的作用及机制研究
SCD1 inhibitor CAY-10566 sensitizes cisplatin by inducing ferroptosis in oral squamous cell carcinoma cells
摘要
Abstract
AIM:To investigate how the stearoyl-CoA desaturase-1(SCD1)inhibitor CAY-10566 induc-es ferroptosis in oral squamous cell carcinoma(OS-CC)cells and enhances their sensitivity to cisplatin,with preliminary exploration of the underlying mo-lecular mechanisms.METHODS:Bioinformatics analysis and clinical specimens were used to evalu-ate SCD1 expression in OSCC tissues.OSCC cell lines(Cal27 and HSC3)were treated with CAY-10566,cis-platin,the ferroptosis inhibitor Ferrostatin-1(Fer-1),or their combinations.Cell viability was assessed using the CCK-8 assay,while reactive oxygen spe-cies(ROS)and lipid ROS levels were measured by flow cytometry.Malondialdehyde(MDA)and re-duced glutathione(GSH)levels were quantified us-ing commercial assay kits.Western blotting was performed to analyze the protein expression of glu-tathione peroxidase 4(GPX4),mechanistic target of rapamycin(mTOR),mature sterol regulatory ele-ment-binding protein 1(m-SREBP1),SCD1,and heme oxygenase 1(HMOX1).RESULTS:SCD1 was significantly overexpressed in OSCC tissues(P＜0.01).Combined treatment with CAY-10566 and cis-platin markedly reduced OSCC cell viability(P＜0.01)and increased lipid peroxidation(P＜0.001),while suppressing GPX4 expression-effects that were re-versed by Fer-1(P＜0.001).CAY-10566 upregulated HMOX1 expression and inhibited mTOR,m-SREBP1,and SCD1 protein levels(P＜0.001).CONCLUSION:CAY-10566 promotes ferroptosis and cisplatin sensi-tivity in OSCC cells,potentially through HMOX1 up-regulation and suppression of the mTOR/SREBP1/SCD1 axis.关键词
铁死亡/口腔鳞癌/脂质过氧化Key words
ferroptosis/oral squamous cell carci-noma/lipid peroxidation分类
医药卫生引用本文复制引用
王之恒,邢新,陶桃,孟恋亲,王君,郭平,柴琳..SCD1抑制剂CAY-10566通过诱导口腔鳞癌细胞铁死亡增敏顺铂的作用及机制研究[J].中国临床药理学与治疗学,2025,30(8):1009-1016,8.基金项目
安徽省高校科学研究重大项目(KJ2021ZD0103) （KJ2021ZD0103）
安徽省大学生创新创业训练计划项目(S202310368046) （S202310368046）
芜湖市科技局应用基础研究项目(2022jc68) （2022jc68）
皖南医学院校重点项目科研基金(WK2024ZZD25) （WK2024ZZD25）
皖南医学院校中青年项目科研基金(WK2024ZQNZ48) （WK2024ZQNZ48）
