Salvigenin: a natural ally against nasopharyngeal carcinoma's malignant phenotypes and immune evasion

Nasopharyngeal carcinoma (NPC) is a prevalent malignancy in Southeast Asia, particularly in southern China. Salvigenin is a natural compound with anti-inflammatory, antioxidant, and anti-tumor properties. The purpose of this research is to explore how Salvigenin impacts the malignant characteristics and immune evasion of NPC cells, as well as to clarify the molecular mechanisms involved. The viability and invasion of NPC cells (HK-1 and C666-1) were assessed using CCK-8 assays and Transwell assays, respectively. The expressions of epithelial-mesenchymal transition (EMT) markers and proteins in AKT/NF-κB pathway were analyzed by Western blot. Additionally, the impact of Salvigenin on tumor growth and immune evasion was examined in a xenograft mouse model. Salvigenin significantly inhibited proliferation and invasion of NPC cells in a dose-dependent manner. Besides, Salvigenin reduced the expression of PD-L1, inhibited CD8 + T cell apoptosis, and increased IFN-γ secretion, indicating attenuation of immune escape. After administration of Salvianin, the IFN-γ⁺ subpopulation was increased, but the TIM-3⁺ subpopulation was significantly reduced, indicating that Salvianin can inhibit T cell depletion. Mechanistically, Salvigenin inhibited the activity of AKT/NF-κB pathway, as evidenced by decreased levels of p-AKT and p-NF-κB. In addition, Salvigenin reduced tumor growth and immune evasion in vivo. Salvigenin exerts anti-tumor effects in NPC by inhibiting proliferation, invasion, EMT, and immune evasion via inactivation of the AKT/NF-κB pathway. Our findings illustrate that Salvigenin has potential as a new treatment option for NPC.