Irisin reverses the IL-6 induced epithelial-mesenchymal transition in osteosarcoma cell migration and invasion through the STAT3/Snail signaling pathway.

ABSTRACT

As a novel discovered myokine, irisin is considered to be a promising candidate for the treatment of metabolic disorders and cancer. However, little is known about the anti-metastasic effect of irisin on osteosarcoma cells and its underlying mechanisms. In the present study, we aimed to explore the effect of irisin on the migration and invasion of osteosarcoma cells and the underlying mechanisms involved. Viability and proliferation of osteosarcoma cells were examined by MTT assay. Then, by using scratch wound healing assay and Transwell assays, we evaluated migratory and invasive ability of the cells, respectively. Moreover, the expression of epithelial-to-mesenchymal transition (EMT) markers were determined by qPCR, western blot and immunofluorescence staining after treatment with IL-6 and irisin. Furthermore, the expression of ERK, p38, STAT3 and Snail were detected by western blot analysis. Finally, an inhibitor of STAT3, WP1066 was applied to testify the effect of irisin on the expression of EMT markers and Snail. It was found that irisin treatment significantly suppressed the proliferation, migration and invasion of osteosarcoma cells. Furthermore, irisin reversed the IL-6-induced epithelial­mesenchymal transition (EMT) in osteosarcoma cells by regulating the expression of E-cadherin, N-cadherin, vimentin, fibronectin, MMP-2, MMP-7 and MMP-9. In addition, irisin suppressed the IL-6-activated phosphorylation of STAT3 and the expression of Snail in osteosarcoma cells. Finally, blockade of STAT3 by WP1066 (a STAT3 inhibitor) further enhanced the effect of irisin on the EMT and Snail expression in osteosarcoma cells. Collectively, our findings revealed that irisin may play a critical role in the IL-6-induced EMT of osteosarcoma cells via the STAT3/Snail signaling pathway.