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

doi:10.12092/j.issn.1009-2501.2025.08.001

中国临床药理学与治疗学 ›› 2025, Vol. 30 ›› Issue (8): 1009-1016.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

王之恒¹, 邢新¹, 陶桃², 孟恋亲¹, 王君¹, 郭平¹, 柴琳²

¹皖南医学院第一附属医院（弋矶山医院）口腔颌面外科,芜湖 241001,安徽;
²皖南医学院口腔医学院,芜湖 241002,安徽

收稿日期:2025-07-04 修回日期:2025-07-10 发布日期:2025-08-12
通讯作者: 柴琳,教授,硕士生导师,从事口腔医学临床、教学和科研工作。E-mail： 869319562@qq.com
作者简介:王之恒,男,副主任医师,研究方向：口腔鳞癌基础与临床研究。E-mail： 20111040@wmmc.edu.cn
基金资助:
安徽省高校科学研究重大项目（KJ2021ZD0103）; 安徽省大学生创新创业训练计划项目（S202310368046）; 芜湖市科技局应用基础研究项目（2022jc68）; 皖南医学院校重点项目科研基金（WK2024ZZD25）; 皖南医学院校中青年项目科研基金（WK2024ZQNZ48）

SCD1 inhibitor CAY-10566 sensitizes cisplatin by inducing ferroptosis in oral squamous cell carcinoma cells

WANG Zhiheng, XING Xin, TAO Tao, MENG lianqin, WANG Jun, GUO Ping, CHAI Lin

¹Department of Oral and Maxillofacial Surgery, the First Affiliated Hospital of Wannan Medical College, Yijishan Hospital, Wuhu 241001, Anhui, China;
²School of Stomatology, Wannan Medical College, Wuhu 241002, Anhui, China

Received:2025-07-04 Revised:2025-07-10 Published:2025-08-12

摘要/Abstract

摘要： 目的：探讨硬脂酰辅酶A去饱和酶-1（SCD1）抑制剂CAY-10566能否诱导口腔鳞癌（oral squamous cell carcinoma,OSCC）细胞铁死亡并增加其对顺铂（DDP）的敏感性,初步探索其相关分子机制。方法：通过生信分析、收集临床标本评价SCD1在OSCC组织中的表达情况,将OSCC细胞Cal27和HSC3分别经过CAY-10566、DDP或铁死亡抑制剂Fer-1处理或联合处理后,通过CCK-8检测细胞存活率,通过流式细胞术检测活性氧（ROS）以及脂质ROS水平,通过丙二醛（MDA）试剂盒、还原性谷胱甘肽（GSH）检测试剂盒检测MDA、GSH水平,Western blot检测谷胱甘肽过氧化物酶4（GPX4）、哺乳动物雷帕霉素靶蛋白（mTOR）、成熟形式的甾醇调节元件结合蛋白1（mature SREBP1,m-SREBP1）、SCD1、血红素加氧酶1（HMOX1）蛋白表达。结果：SCD1在OSCC组织中显著高表达（P<0.01）,CAY-10566与DDP联合处理后,OSCC细胞活性显著下降（P<0.01）,脂质过氧化水平上升（P<0.001）,GPX4表达被抑制,这一作用效果能被Fer-1所逆转（P<0.001）,CAY-10566增加OSCC细胞内HMOX1的表达,并抑制mTOR、m-SREBP1、SCD1蛋白的表达（P<0.001）。结论：CAY-10566能够诱导OSCC细胞铁死亡并增敏DDP作用,作用机制可能与上调HMOX1以及对mTOR/SREBP1/SCD1轴的抑制有关。

关键词: 铁死亡, 口腔鳞癌, 脂质过氧化

Abstract: AIM: To investigate how the stearoyl-CoA desaturase-1 (SCD1) inhibitor CAY-10566 induces ferroptosis in oral squamous cell carcinoma (OSCC) cells and enhances their sensitivity to cisplatin, with preliminary exploration of the underlying molecular mechanisms. METHODS: Bioinformatics analysis and clinical specimens were used to evaluate SCD1 expression in OSCC tissues. OSCC cell lines (Cal27 and HSC3) were treated with CAY-10566, cisplatin, the ferroptosis inhibitor Ferrostatin-1 (Fer-1), or their combinations. Cell viability was assessed using the CCK-8 assay, while reactive oxygen species (ROS) and lipid ROS levels were measured by flow cytometry. Malondialdehyde (MDA) and reduced glutathione (GSH) levels were quantified using commercial assay kits. Western blotting was performed to analyze the protein expression of glutathione peroxidase 4 (GPX4), mechanistic target of rapamycin (mTOR), mature sterol regulatory element-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 cisplatin markedly reduced OSCC cell viability (P<0.01) and increased lipid peroxidation (P<0.001), while suppressing GPX4 expression-effects that were reversed 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 sensitivity in OSCC cells, potentially through HMOX1 upregulation and suppression of the mTOR/SREBP1/SCD1 axis.

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

中图分类号:

R965.2

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.

WANG Zhiheng¹, XING Xin¹, TAO Tao², MENG lianqin¹, WANG Jun¹, GUO Ping¹, CHAI Lin². SCD1 inhibitor CAY-10566 sensitizes cisplatin by inducing ferroptosis in oral squamous cell carcinoma cells[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2025, 30(8): 1009-1016.

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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

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