SNX-2112 Induces Apoptosis and Inhibits Proliferation, Invasion, and Migration of Non-Small Cell Lung Cancer by Downregulating Epithelial-Mesenchymal Transition via the Wnt/β-Catenin Signaling Pathway.

Abstract

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/β-catenin signaling pathway (glycogen synthase kinase (GSK) 3β and phosphorylated (p)-β-catenin increased, β-catenin and p-GSK3β decreased) in NSCLC cells. These results were verified by rescue experiments using a Wnt/β-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/β-catenin signaling pathway.

• Authors: Xiaozhen Cheng, Lingyu Qin, Lian Deng, Xiongjie Zhu, Ying Li, Xiaoran Wu, Yanfang Zheng
• Journal: Journal of Cancer (J Cancer) Vol. 12 Issue 19 Pg. 5825-5837 ( 2021) ISSN: 1837-9664 [Print] Australia
• PMID: 34475996 (Publication Type: Journal Article)
• Copyright: © The author(s).