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

Oral tongue squamous cell carcinoma (OTSCC), the most prevalent oral malignancy, lacks effective treatments. Evaluate Evodia lepta (E. lepta) as a potential OTSCC therapeutic. Cell viability (CCK-8) and protein expression (Western blot) were assessed in OTSCC (CAL27, TCA8113) and 3T3 cells after 24h treatment with E. lepta or cisplatin. Cisplatin significantly reduced the viability in all cells (IC50: 3T3 = 9.5 μM; CAL27/TCA8113 = 3.5 μM). E. lepta selectively targeted OTSCC cells (IC50: CAL27 = 80 μg/mL; TCA8113 = 60 μg/mL) with no 3T3 toxicity. Protein expression analysis revealed that E. lepta 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 E. lepta. E. lepta 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.