Effect Of Decarbromodiphenyl Ether(BDE-209) On Metastatic Ability Of Triple-Negative Breast Cancer Cells And Its Mechanism

ObjectiveTriple negative breast cancer(TNBC)is the most aggressive subtype of breast cancer with high probability of metastasis.Decarbromodiphenyl ether(BDE-209)is a new persistent organic pollutants(POPs)which is regarded as an independent risk factor for breast cancer,but its potential effects on TNBC metastasis have so far received less focus.In the present study,we investigate the effect of BDE-209 exposure on the metastasis of TNBC cells in vitro and its molecular mechanism involved.MethodsCell viability was evaluated using the CCK-8 assay.The MDA-MB-231 cells were cultured in induction medium in the presence of different doses of BDE-209.We measured the effect of BDE-209 on the metastasis of MDA-MB-231 by wound-healing assay and transwell test.The protein level of STAT3(signal transducers and activators of transcription 3)and p-STAT3 were determined by WB and immunohistochemistry.A murine spontaneous metastasis model,in which BDE-209-exposded-TNBC 4T1 cells were injected into the left armpit of Bal b/c mice,was used to examine the effetcs of BDE-209 on lung metastasis lesions.Results1.BDE-209 exposures significantly promoted metastasis of MDA-MB-231 cells in a dose-dependent manner..2.Compared with the control group,tumor size and tumor weight were significantly increased in BDE-209 exposure group.3.Seven days after injection of mouse TNBC cell line 4T1 exposed to BDE-209,33%of mice developed lung metastasis,which was significantly higher than that of 4T1 cells without BDE-209 exposure(17%).4.BDE-209 exposure significantly increased the expression of STAT3 and phosphorylated STAT3 in TNBC cell line MDA-MB-231.5.After the inhibition of STAT3 signal pathway by STAT3 inhibitor(STAT3-IN-1,S0818),the increased MDA-MB-231 migration ability after BDE-209 exposure was significantly inhibited.Conclusion1.BDE-209 exposure could promote metastasis potential of TNBC cell line MDA-MB-231 in dose dependent manner.2.BDE-209 exposure could promote metastasis potential of TNBC cell via STAT3 signaling.