Snx-2112 Induces Apoptosis And Inhibits Proliferation, Invasion, And Migration Of Non-Small Cell Lung Cancer By Downregulating Epithelial-Mesenchymal Transition Via The Wnt/Beta-Catenin Signaling Pathway

Lung cancer is the most frequent malignant tumor, and non-small cell lung cancer (NSCLC) is responsible for substantial mortality worldwide. The small molecule SNX-2112 was recently shown to critically effect the proliferation and apoptosis of tumor cells. Nevertheless, the precise mechanism by which SNX-2112 affects NSCLC remains poorly understood. Therefore, we investigated the function of SNX-2112 in NSCLC. We verified that SNX-2112 promoted apoptosis and suppressed the proliferation, invasion, and migration of A549 and H520 NSCLC cells in vitro. We further verified the potential mechanism of SNX-2112 in NSCLC. The changes in the protein levels demonstrated that SNX-2112 inhibited the epithelial-mesenchymal transition (EMT) (increased E-cadherin and decreased N-cadherin and vimentin) and the Wnt/beta-catenin signaling pathway (glycogen synthase kinase (GSK) 3 beta and phosphorylated (p)-beta-catenin increased, beta-catenin and p-GSK3 beta decreased) in NSCLC cells. These results were verified by rescue experiments using a Wnt/beta-catenin pathway agonist. We also established a tumor xenograft model and confirmed that SNX-2112 reduced tumor growth and proliferation and enhanced necrosis and apoptosis in a NSCLC model in vivo. In conclusion, the current study is the first to discover the mechanism of SNX-2112 in NSCLC. SNX-2112 induced apoptosis and also inhibited the proliferation, invasion, and migration of NSCLC cells by downregulating EMT via the Wnt/beta-catenin signaling pathway.