Targeting Cd36 Inhibits Olk Progression Under High-Fat Conditions

Obesity-induced lipid metabolism dysregulation plays a significant role in the progression and poor prognosis of oral squamous cell carcinoma, but its impact on the malignant transformation of oral leukoplakia (OLK) remains unclear. This study aims to provide new insights and theoretical support for the daily intervention and management of obese OLK patients. Approved by the Laboratory Animals Ethics Committee of Sun Yat-sen University, this study established a high-fat diet (HFD) and 4-Nitroquinoline-1-oxide-induced oral mucosal malignant transformation model in 6-8-week-old male C57 mice, with the human dysplastic oral keratinocytes (DOK) employed for in vitro experiments. Experimental methods comprised qPCR, Western blot, CCK-8 assay, Transwell migration assay, wound healing assay, H&E staining, and immunohistochemistry. Data analysis was performed using GraphPad Prism (version 8.2) with Student's t-test and ANOVA (P < 0.05). Exogenous fatty acids promote DOK cells proliferation, migration, and upregulate CD36 expression. The exogenous fatty acid-induced enhancement of DOK cells proliferation and migratory capacity in vitro was significantly suppressed through CD36 inhibition. Administration of CD36-blocking antibodies mitigated HFD-aggravated OLK hyperplasia in murine models. Inhibition of CD36 significantly attenuates the promoting effects of exogenous fatty acids on the malignant behavior of DOK cells, and targeting CD36 inhibits the HFD-induced promotion of OLK development and progression in murine models, suggesting CD36 as a potential therapeutic target.