Curcumin inhibits vascular mimicry to prevent thyroid cancer progression through regulation of EPH receptor A2/phosphoinositide 3-kinase

Abstract

This study explored the impact of curcumin on vascular mimicry in thyroid cancer (TC) cells and underlying mechanism. TC cells (TPC-1) were exposed to curcumin at 15 and 30 μmol/L (low-dose and high-dose group) concentrations, respectively, with control group exposed to culture medium. After treatment, cell migration, invasion, proliferation and apoptosis were detected along with analysis of EphA2 and PI3K expressions. The amount of migrated and invaded cells, EphA2 and PI3K protein expressions, Matrix metalloproteinase 2(MMP2), MMP9, CyclinD1, EphA2 and PI3K of TPC-1 cells in curcumin groups were decreased (P < 0.05). Apoptosis, as well as Cleaved-caspase-3, Bax and p21 expressions increased (P < 0.05). Curcumin dose-dependently suppressed angiogenesis of TPC-1 cells (P < 0.05) and lumen formation. In addition, TPC-1 cells showed cell rearrangement and scattered tubules after conditioned medium of neurotrophic factor (NTF-CM) treatment, while the CM of cancer-associated fibroblasts (CAF-CM) (50%) and CAF-CM (100%) both significantly promoted vasculogenic mimicry in TPC-1 cells, with elevated amount of tubules and junctions (P < 0.05). Moreover, treatment with ALW-II-41-27, which is an EphA2 inhibitor, alleviated the CAF-CM’s effect on vasculogenic mimicry (P < 0.05), and EphA2 knockdown decreased MMP2, MMP9, EphA2 and PI3K protein expressions when decelerating tube formation in NTF-CM and CAF-CM groups (P < 0.05). Collectively, Curcumin suppresses malignant behaviors and hinders vascular mimicry of TC cells by inhibiting the EPHA2/PI3K pathway, thereby preventing malignant progression of TC.