Estrogen receptor β exhibited anti-tumor effects on osteosarcoma cells by regulating integrin, IAP, NF-kB/BCL-2 and PI3K/Akt signal pathway

Abstract

This study aimed to investigate the effects of Estrogen receptor β (ERβ) on osteosarcoma cells, and explore the regulatory mechanisms involved in this process. Osteosarcoma U2-OS cells consisted four groups, and treated by E2, E2 + LY294002 (ERβ agonists), E2 + ERβ siRNA, E2 + ERβ siRNA + LY294002, respectively. Cell counting kit 8 (CCK-8) assay was performed to detect the cell viability of U2-OS cells in each group. The effects of ERβ on the migration and invasion ability of U2-OS cells were examined by wound healing assay and transwell cell culture chamber, respectively. The expression of Inhibitor of apoptosis protein (IAP) and integrin α5 in U2-OS cells of each group was detected by quantitative RT-PCR, and the expression of phosphorylated p65 (p-p65), p-AKT and Bcl-2 was detected by western blotting. The cell viability, migration and invasion ability of U2-OS cells were significantly increased by ERβ siRNA, but inhibited by ERβ agonists LY294002 (p < 0.05). ERβ siRNA significantly downregulated Integrin α5 and unregulated IAP in U2-OS cells (p < 0.05). The expression of p-p65, p-AKT and Bcl-2 was significantly reduced by LY294002, but increased by ERβ siRNA (p < 0.05). In conclusion, ERβ exhibited obvious anti-tumor effects on osteosarcoma cells by regulating integrin, IAP, NF-kBBCL-2 and PI3K/Akt signal pathway.