Decarbromodiphenyl ether (BDE-209) exposure promotes migration of triple-negative breast cancer cells through STAT3 signaling pathway

Objective To explore the exposure of decarbromo diphenyl ether (BDE-209), a new persistent organic pollutant (POP) with the highest level in human body, on the migration of triple-negative breast cancer (TNBC) cell line MDE-MB-231, and explore the effects of its exposure on the development of TNBC and underlying mechanism in the process. Methods MDA-MB-231 cells were divided into blank control group (high glucose DMEM), solvent control group (2% DMSO in high glucose DMEM) and BDE-209 exposure groups (0.02, 0.2, 2, 20, 200 and 2 000 ng/mL BDE-209 in high glucose DMEM).In 24 h after culture, CCK-8 assay was used to determine the IC50 value of BDE-209.Scratch wound assay and Transwell assay were employed to determine the effect of BDE-209 exposure on migration ability of MDA-MB-231 cells.The protein levels of signal transducers and activators of transcription 3(STAT3) and its phosphorylation level (p-STAT3) were detected with Western blotting and immunocytochemical assay.The effect of BDE-209 exposure on the expression and activation of STAT3 in tumor-bearing mice with transplantation of 4T1 cells. Results BDE-209 exposure significantly promoted the migration of MDA-MB-231 cells, in a dose-dependent manner, when compared with blank control cells (P < 0.01).Western blotting and immunocytochemical assay showed that BDE-209 exposure enhanced the expression of STAT3 and p-STAT3 in MDA-MB-231 cells (P < 0.05).In tumor-bearing mice, the expression levels of STAT3 and p-STAT3 were obviously enhanced in the TNBC tissues after exposure to 200 ng/mL BDE-209.While, treatment of STAT3 inhibitor STAT3-IN-1 could notably suppress the migration of MDA-MB-231 cells induced by BDE-209 exposure (P < 0.001). Conclusion BDE-209 exposure promotes the migration ability of TNBC cells via up-regulation and activation of STAT3, and thus improve the metastasis.