A novel O2- (2,4-dinitrophenyl) diazeniumdiolate inhibits hepatocellular carcinoma migration, invasion, and EMT through the Wnt/β-catenin pathway

Targeted Wnt/β-catenin pathway is considered to be a promising therapy for cancer metastasis. The novel O2 -(2,4-dinitrophenyl) diazeniumdiolate (JS-K) plays a potent inhibitory role in the proliferation of cancers. In this study, HepG2 and SMMC7721 were used to clarify the efficacy of JS-K inhibition of HCC metastasis. JS-K significantly inhibited cell motility through a wound-healing assay and restrained cell migration and invasion at noncytotoxic concentrations. However, the inhibitory effects of migration and invasion were abolished after the addition of NO scavenger, Carboxy-PTIO. In addition, JS-K inhibited the Wnt/β-catenin pathway by a decrease of p-GSK-3β at Ser9, cytosolic β-catenin, and nuclear β-catenin accumulation whereas an increase of p-β-catenin. Furthermore, the transcription regulators c-Myc, survivin, and Cyclin D1 were down-regulated after treating with JS-K. The inhibitory of the Wnt/β-catenin pathway was reversed after the addition of Carboxy-PTIO or LiCl. Meanwhile, JS-K also inhibited the epithelial-mesenchymal transition (EMT)-mediated cell migration and invasion. The characteristics of the inhibition were reflected by the upregulation of E-cadherin whereas the downregulation of Vimentin, Snail, and Slug. Taking together, these results demonstrated that JS-K inhibited HepG2 and SMMC7721 cells migration and invasion by reversing EMT via the Wnt/β-catenin pathway.