Medicarpin suppresses thyroid cancer progression by inhibiting the AKT/NF-κB pathway and enhancing CD8+ T cell-mediated antitumor immunity.

BACKGROUND

Poorly differentiated and anaplastic thyroid cancers exhibit resistance to treatment and immune evasion. Medicarpin (MED), a natural pterocarpan derived from leguminous plants, has shown anticancer activity in multiple tumor models. This study investigated the effects of MED on thyroid cancer progression.

METHODS

Thyroid cancer cell lines (8505 C, TPC-1) and normal thyroid epithelial cells (Nthy-ori 3-1) were treated with varying concentrations of MED. Proliferation, apoptosis, and protein expression were evaluated using CCK-8, Hoechst staining, flow cytometry, ELISA, Western blot, and immunofluorescence. Tumor-immune interactions were assessed via co-culture with CD8+ T cells. The AKT activator SC79 was used to verify the involvement of the pathway. In vivo effects were analyzed in humanized NOG mice bearing subcutaneous 8505 C xenografts.

RESULTS

No cytotoxicity was observed in Nthy-ori 3-1 cells treated with MED at concentrations ≤80 μM. but MED reduced cell viability in 8505 C and TPC-1 cells (IC50: 62.20 μM for 8505 C, 70.84 μM for TPC-1). Apoptosis was confirmed by nuclear fragmentation and an increase in cleaved caspase-3. MED suppressed PD-L1 expression and CD8+ T cell apoptosis, while enhancing IFN-γ, TNF-α, and Granzyme B secretion. MED reduced phosphorylation and nuclear translocation of NF-κB via AKT inhibition, which SC79 partially reversed. In vivo, MED reduced tumor growth in humanized NOG mice, decreased PD-L1 and AKT/NF-κB signaling, enhanced CD8+ T-cell activation (CD69, IFN-γ), indicating immune-dependent antitumor activity.

CONCLUSIONS

MED suppresses thyroid cancer progression by inhibiting proliferation and immune evasion through the inactivation of AKT/NF-κB, supporting its potential as a therapeutic candidate.