2019 Volume 44 Issue 4 Pages 237-244
Di(2-ethylhexyl) phthalate (DEHP) is widely used in polyvinylchloride-based materials and remains intact in the environment. Lungs are one route of entry of DEHP into the body; however, there is limited information on the effects and mechanism of action of DEHP on non-small cell lung cancer (NSCLC). Here, we addressed this by examining the effect of DEHP on the proliferation of A549 human lung adenocarcinoma cells by MTS assay. The induction of inflammation and epithelial-to-mesenchymal transition (EMT), as well as activation of the mitogen-activated protein kinase (MAPK) and Wnt/β-catenin signaling pathways, were assessed by western blot and real-time polymerase chain reaction. Although there were discrepancies in the concentration, DEHP treatment enhanced A549 cell viability accompanied by increased mRNA and protein levels of inflammation-related factors, such as matrix metalloproteinase-9 and nuclear factor-κB. Additionally, EMT was activated in cells according to decreased E-cadherin and increased vimentin expression. Furthermore, MAPK pathway components, including phosphorylated p38 and c-Jun N-terminal kinase, and Wnt/β-catenin pathway components, including phosphorylated glycogen synthase kinase 3β and β-catenin, as well as their downstream genes c-Myc and cyclin D1, were upregulated in the presence of DEHP. These results suggest that DEHP promotes NSCLC progression by promoting cell proliferation, inflammation, and EMT via activation of Wnt/β-catenin signaling.
