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

doi:10.12092/j.issn.1009-2501.2025.08.001

Abstract

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

CLC Number:

R965.2

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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