The Chemotherapy Medication of (Spreng). Merr. on the Viability of Tongue Cancer Cells Through the PD-L1/MMP14/HSPA5 Pathway.

Background: Oral tongue squamous cell carcinoma (OTSCC), the most prevalent oral malignancy, lacks effective treatments.

Objective: Evaluate Evodia lepta ( ) as a potential OTSCC therapeutic.

Methods: Cell viability (CCK-8) and protein expression (Western blot) were assessed in OTSCC (CAL27, TCA8113) and 3T3 cells after 24h treatment with or cisplatin.

Results: Cisplatin significantly reduced the viability in all cells (IC: 3T3 = 9.5 μM; CAL27/TCA8113 = 3.5 μM). selectively targeted OTSCC cells (IC: CAL27 = 80 μg/mL; TCA8113 = 60 μg/mL) with no 3T3 toxicity. Protein expression analysis revealed that downregulated GPX4, ADRM1, MMP14, PD-L1, and HSPA5 in both CAL27 and 3T3 cells. Interestingly, the expression of p17 exhibited divergent regulation between cell types. In contrast, cisplatin treatment upregulated GPX4 and downregulated MMP14, PD-L1, and HSPA5 in CAL27 cells, with p17 regulation opposing that observed with .

Conclusion: selectively induces ferroptosis through GPX4 and HSPA5 downregulation, demonstrating multi-target effects including proteostasis disruption (ADRM1), metastasis inhibition (MMP14), and immune evasion suppression (PD-L1). Its GPX4 suppression contrasts with cisplatin's upregulation, suggesting utility in cisplatin-resistant OTSCC. PD-L1 reduction implies immunotherapeutic potential, meriting further study.