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-  2019 

Spherical silica nanoparticles promote malignant transformation of BEAS

DOI: 10.1177/0300060518814333

Keywords: Benzopyrene,silica nanoparticles,inflammation,epithelial-mesenchymal transition,lung cancer,stromal cell-derived factor-1α,AKT pathway

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Abstract:

This study aimed to examine the role of spherical silica nanoparticles (SiNPs) on human bronchial epithelial (BEAS-2B) cells through inflammation. Human mononuclear (THP-1) cells and BEAS-2B cells were co-cultured in transwell chambers and treated with 800?mmol/L benzo[a]pyrene-7, 8-dihydrodiol-9, 10-epoxide (BPDE) and 12.5?μg/mL SiNPs for 24 hours. For controls, cells were treated with BPDE alone. Subcutaneous tumorigenicity and epithelial-mesenchymal transition (EMT) of BEAS-2B cells were measured. The cells were blocked with a stromal cell-derived factor-1α (SDF-1α)-specific antibody. EMT was analyzed in cells treated with 800?mmol/L BPDE and 12.5?μg/mL SiNPs relative to matched control cells and xenografts in vivo. Serum SDF-1α levels were measured in 23 patients with lung adenocarcinoma in Xuanwei, in 25 with lung adenocarcinoma outside Xuanwei, and in 22 with benign pulmonary lesions in Xuanwei. SiNPs significantly promoted tumorigenesis and EMT, induced the release of SDF-1α, and activated AKT (ser473) in BEAS-2B cells. EMT and phosphorylated AKT (ser473) and glycogen synthase kinase-3β levels were decreased when blocked by SDF-1α antibody in BEAS-2B cells. SDF-1α was mainly secreted by THP-1 cells. SiNPs combined with BPDE promote EMT of BEAS-2B cells via the AKT pathway by inducing release of SDF-1α from THP-1 cells

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