Immunopharmacology and immunotoxicology · 2026
Medicarpin suppresses thyroid cancer progression by inhibiting the AKT/NF-κB pathway and enhancing CD8+ T cell-mediated antitumor immunity.
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Zhang Zhitao, Zhang Xu, Yu Yinping, Zhang Xiaoming
Аннотация
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.
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.