Effects of Chronic Exposure to Low-concentration Tetrabromobisphenol A on the Proliferation of Breast Cancer Cells
Tetrabromobisphenol A(TBBPA)is the reactive and additive brominated flame retardants(BFRs)with the highest production volume,which has the characteristics of persistent organic pollutants and can be exposed to human bodies in various ways.Thus,the relationship between TBBPA exposure and human health risks needs to be studied urgently.In particular,as a potential environmental estrogen disruptor,the carcinogenic mechanism of TBBPA on estrogen-sensitive breast cancer cells remains unclear.Therefore,in this study,human MCF-7(ER-positive)cell lines and MDA-MB-231(ER-negative)cell lines were continuously treated with the actual plasma concentration of TBBPA(10-8 mol/L)for five generations to simulate long-term exposure mode.The proliferation effect and the possible mechanism were examined.The data from CCK8 and colony formation experiments demonstrated that 10-8 mol/L TBBPA long-term exposure promoted the proliferation of MCF-7 cells.The content of ROS increased in MCF-7 cells after long-term exposure to 10-8 mol/L TBBPA.Western blotting results showed that 10-8 mol/L TBBPA upregulated the Ras expression and induced p-ERK1/2,c-Myc,and Cyclin D1 expression in MCF-7 cells on long-term exposure.Moreover,the intervention of Ras inhibitor FTS blocked the Ras/p-ERK1/2/Cyclin D1/c-Myc and inhibited cell proliferation.In addition,the data from CCK8 showed that pretreatment of MCF-7 cells by Fulvestrant,an ERα inhibitor,could attenuate cell proliferation activity induced by TBBPA,suggesting that the promotion of MCF-7 cell proliferation by TBBPA was directly related to the ER.At the same time,the MDA-MB-231(ER-negative)cell line was selected for research.Under long-term exposure to the same concentration of TBBPA,its proliferation activity,ROS level,and Ras signaling pathway related proteins were not significantly affected.These results show that long-term exposure to 10-8 mol/L TBBPA can accelerate MCF-7(ER-positive)cell proliferation via the activation of the Ras signaling pathway.
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