Asperuloside Restrained Non-Small Cell Lung Cancer Progression via Repressing TGF-β1/Smad2 Signaling Pathway

Abstract

Background: Asperuloside has an antitumor effect on various cancers, but its relationship with non-small cell lung cancer (NSCLC) has yet to be established. Hence, the aim of this study was designed to explore the action and mechanism of Asperuloside on NSCLC. Methods: After A549 and H226 cells were treated with Asperuloside (1, 2, 3, 4, 5 and 10 mM), transforming growth factor-β1 (TGF-β1) or SB431542 (TGF-β1/Smad signal inhibitor) or not, cell biological behaviors were detected by 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide (MTT), flow cytometry, colony formation, Transwell, and scratch assays. The tumor xenograft model was established in nude mouse, and the size and weight of tumors were measured. The levels of proteins related to epithelial-mesenchymal transition (EMT) and TGF-β1/mothers against decapentaplegic homolog 2 (Smad2) signaling in treated NSCLC cells and mouse tumors were quantified using Western blot. Results: Asperuloside significantly dampened the viability as well as abilities to proliferate, invade and migrate, while facilitating apoptosis of A549 and H226 cells, and significantly decreased mouse tumor size and weight. Asperuloside and SB431542 significantly down-regulated the protein levels of TGF-β1, p-Smad2, N-Cadherin and Vimentin, but up-regulated E-Cadherin protein level in treated A549 and H226 cells and mouse tumors. However, TGF-β1 had the opposite effect on NSCLC cells. Besides, the impact of TGF-β1 upon the A549 and H226 cells was inhibited by Asperuloside and SB431542. Conclusions: Asperuloside represses the malignant capabilities of NSCLC cells both in vitro and in vivo by inhibiting TGF-β1/Smad2 pathway.