Evodiamine inhibits programmed cell death ligand 1 expression via the PI3K/AKT signaling pathway to regulate antitumor immunity in melanoma.

Abstract

Malignant melanoma, a rare and aggressive skin cancer, arises from the transformation of cutaneous melanocytes and is associated with a poor prognosis. Evodiamine (EVO), a bioactive compound derived from traditional Chinese herbal medicine, has demonstrated significant inhibitory effects on various tumor cells. In this study, we aimed to investigate the potential of EVO in regulating melanoma immunity and elucidate its underlying mechanisms. Experimental results revealed that the IC₅₀ value of EVO in B16-F10 cells for 24, 48, and 72 h were 11.73, 5.083, and 4.604 µM, respectively. EVO inhibited the proliferation, invasion, and metastasis of B16-F10 cells by more than 50%, while promoting apoptosis of higher concentration of EVO. EVO also significantly suppressed tumor growth by more than 80% and reduced spleen damage in tumor-bearing mice. Treatment with EVO led to a marked increase in T-cell subsets in the spleen, bone marrow, and tumors, with immunohistochemical (IHC) staining in particular showing about 50% higher. Furthermore, EVO inhibited the expression of programmed cell death ligand 1 (PD-L1) and the PI3K/AKT signaling pathway-related proteins in both B16-F10 cells and tumors. These findings suggest that EVO exerts antitumor effects by enhancing the tumor immune microenvironment and indicates its potential as a therapeutic agent for melanoma.