NDRG1 suppresses TGF-β-induced epithelial-mesenchymal transition in lung cancer A549 cells

Abstract

Objective To explore the effect and molecular mechanism of N-myc downstream regulated gene 1 (NDRG1) on transforming growth factor-beta (TGF-β)-induced epithelial-mesenchymal transition (EMT) in human lung cancer cells. Methods Lung cancer A549 cells were transfected with NDRG1 overexpressed vector, and then treated with 5 μg/L TGF-β1. The abilities of invasion were detected by Transwell assay. The expressions of NDRG1 mRNA and protein were analyzed by teal-time reverse transcription polymerase chain reaction (RT-PCR) were examined with Western blot. The expressions of EMT-associated markers E-cadherin and Vimentin, and EMT-associated signaling molecules Snail, AKT and Smad were detected with Western blot. Results We found that TGF-β1 treatment could induce morphological alteration of A549 cells from epithelial morphology to mesenchymal morphology. TGF-β1 significantly increased the migration of A549 cells, and increased the expression of mesenchymal maker vimentin and decreased epithelial marker E-cadherin. More importantly, overexpression of NDRG1 significantly reversed the effects of TGF-β1 on A549 cells. Moreover, NDRG1 significantly decreased the levels of phospho-AKT, and suppressed the expression of EMT-related transcription factor Snail. Conclusions NDRG1 could reverse the effects of TGF-β1 on EMT in A549 cells, by which mechanism is related to reduction of the expressions of phospho-AKT and Snail. Key words: Intercellular signaling peptides and proteins/PD/ME; Transforming growth factor beta/AE; Lung neoplasms/PA; Cell transformation, neoplastic/DE; Epithelial cells/DE/PA; Stromal cells/DE/PA