Tilianin regulates the proliferation, invasion and tumor immune microenvironment of thyroid cancer cells through the TLR4/NF-κB axis.

Thyroid cancer is the most prevalent form of endocrine malignancy. Tilianin has demonstrated anti-tumor properties in ovarian cancer and non-small cell lung cancer (NSCLC), while its effects on thyroid cancer progression remain elusive. Hence, this research explored the role of Tilianin in thyroid cancer development and clarified the underlying mechanisms. The findings indicated that Tilianin reduced cell viability of TPC-1 (IC50 = 38.97 μM) and IHH4 (IC50 = 27.69 μM) cells dose-dependently and inhibited the expression of Ki-67. Additionally, Tilianin impaired the invasion capacity of TPC-1 and IHH4 cells, decreased the PD-L1 level, strengthened the CD8+T cell viability, and elevated the secretions of IFN-γ, IL-2, and TNF-α in CD8+T cells. Furthermore, Tilianin could suppress the activation of the TLR4/NF-κB pathway. The inhibitory effects of Tilianin on TPC-1 cell proliferation, invasion, and immune escape were reversed by overexpression of TLR4. In vivo, oral administration of Tilianin restrained thyroid cancer tumor growth, reduced the levels of Ki-67, PD-L1, TLR4, and p-NF-κB, and increased CD8+ T cell levels. In summary, Tilianin effectively restrained thyroid cancer cell proliferation, invasion, and tumor immune microenvironment through inactivating the TLR4/NF-κB pathway.