TGF-β inhibitor RepSox suppresses osteosarcoma via the JNK/Smad3 signaling pathway

Abstract

Osteosarcoma (OS) is the most common malignant bone tumor and the long-term survival rates remain unsatisfactory. Transforming growth factor-β (TGF-β) has been revealed to play a crucial role in OS progression, and RepSox is an effective TGF-β inhibitor. In the present study, the effect of RepSox on the proliferation of the OS cell lines (HOS and 143B) was detected. The results revealed that RepSox effectively inhibited the proliferation of OS cells by inducing S-phase arrest and apoptosis. Moreover, the inhibitory effect of RepSox on cell migration and invasion was confirmed by wound-healing and Transwell assays. Furthermore, western blotting revealed that the protein levels of molecules associated with the epithelial-mesenchymal transition (EMT) phenotype, including E-cadherin, N-cadherin, Vimentin, matrix metalloproteinase (MMP)-2 and MMP-9, were reduced by RepSox treatment. Concurrently, it was also revealed that the JNK and Smad3 signaling pathway was inhibited. Our in vivo findings using a xenograft model also revealed that RepSox markedly inhibited the growth of tumors. In general, our data demonstrated that RepSox suppressed OS proliferation, EMT and promoted apoptosis by inhibiting the JNK/Smad3 signaling pathway. Thus, RepSox may be a potential anti-OS drug.