IL-6 plays a crucial role in epithelial-mesenchymal transition and pro-metastasis induced by sorafenib in liver cancer

Abstract

Interleukin-6 (IL-6) is involved in various biological responses, including tumor progression, metastasis and chemoresistance.However,theroleandmolecularmechanism of IL-6 in the treatment of sorafenib in liver cancer remain unclear. In the present study, through western blot analysis, Transwell assay, flow cytometric assay, ELISA analysis and immunohistochemistry it was revealed that sorafenib promoted metastasis and induced epithelial-mesenchymal transition (EMT) in liver cancer cells in vitro and in vivo, and significantly increased IL-6 expression. Endogenous or exogenous IL-6 affected metastasis and EMT progression in liver cancer cells through Janus kinase 2/signal transducer and activator of transcription 3 (STAT3) signaling. Knocked out IL-6 markedly attenuated the pro-metastasis effect of sorafenib and increased the susceptibility of liver cancer cells to it. In conclusion, the present results indicated that IL-6/STAT3 signaling may be a novel therapeutic strategy for liver cancer.