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

Shangfu XIE; Linming LU; Mengxiao Jiang; Qi WANG; Hui ZHI

doi:10.16016/j.2097-0927.202302085

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

Basic Medicine | 更新时间：2026-01-09

- Decarbromodiphenyl ether (BDE-209) exposure promotes migration of triple-negative breast cancer cells through STAT3 signaling pathway
- Journal of Army Medical University Vol. 45, Issue 17, Pages: 1838-1845(2023)
- 作者机构：
  
  241002 安徽芜湖，皖南医学院病理解剖教研室
- 作者简介：
- 基金信息：
- DOI：10.16016/j.2097-0927.202302085
  CLC： R730.23;R737.9;R994.6
- Received：15 February 2023，
  
  Revised：2023-05-31，
  
  Published：15 September 2023
- 稿件说明：
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Shangfu XIE, Linming LU, Mengxiao Jiang, et al. Decarbromodiphenyl ether (BDE-209) exposure promotes migration of triple-negative breast cancer cells through STAT3 signaling pathway[J]. Journal of Army Medical University, 2023, 45(17): 1838-1845.
DOI：

Shangfu XIE, Linming LU, Mengxiao Jiang, et al. Decarbromodiphenyl ether (BDE-209) exposure promotes migration of triple-negative breast cancer cells through STAT3 signaling pathway[J]. Journal of Army Medical University, 2023, 45(17): 1838-1845. DOI： 10.16016/j.2097-0927.202302085.

摘要

目的

通过检测在人体中含量较高的新型污染物--十溴联苯醚(BDE-209)暴露对三阴性乳腺癌细胞MDE-MB-231迁移能力的影响

探讨BDE-209暴露对三阴性乳腺癌(triple-negative breast cancer

TNBC)发展的影响及其可能的作用机制。

方法

将TNBC细胞MDA-MB-231分为3组: 空白对照组(仅含DMEM高糖培养液)、溶剂对照组(含2% DMSO的DMEM高糖培养液)、BDE-209暴露组(在DMEM高糖培养液中加入0.02、0.2、2、20、200、2 000 ng/mL BDE-209)

暴露24 h后采用CCK-8实验根据半数抑制浓度(IC

)确定BDE-209的暴露浓度。划痕实验与Transwell小室检测BDE-209暴露对MDA-MB-231细胞迁移能力的影响。运用Western blot和细胞免疫组织化检测信号转导和转录活化因子3(signal transducers and activators of transcription 3

STAT3)及其磷酸化(p-STAT3)的表达水平。采用小鼠荷瘤实验检测BDE-209暴露对于TNBC肿瘤组织中STAT3的表达与活化的影响。

结果

与空白对照组比较

BDE-209暴露即可显著提高MDA-MB-231细胞的迁移能力(

0.01)

且呈剂量依赖效应。Western blot和细胞免疫组化检测结果显示

BDE-209暴露显著提高TNBC肿瘤细胞STAT3及p-STAT3的表达(

0.05)。TNBC荷瘤小鼠结果表明STAT3及p-STAT3在BDE-209(200 ng/mL)暴露后TNBC细胞形成的肿瘤组织中表达量均显著提高。以STAT3抑制剂(STAT3-IN-1)抑制STAT3信号通路后

BDE-209暴露后增加MDA-MB-231的迁移能力受到显著抑制(

0.001)。

结论

BDE-209暴露可通过上调STAT3的表达与活化增加TNBC细胞的迁移能力

促进TNBC的转移。

Abstract

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

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 IC

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 (

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 (

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 (

0.001).

Conclusion

BDE-209 exposure promotes the migration ability of TNBC cells

via

up-regulation and activ

ation of STAT3

and thus improve the metastasis.

关键词

Keywords

references

NEDELJKOVIC M, DAMJANOVIC A. Mechanisms of chemotherapy resistance in triple-negative breast cancer—how we can rise to the challenge[J]. Cells, 2019, 8(9): 957. DOI: 10.3390/cells8090957.

GARRIDO-CASTRO A C, LIN N U, POLYAK K. Insights into molecular classifications of triple-negative breast cancer: improving patient selection for treatment[J]. Cancer Discov, 2019, 9(2): 176-198. DOI: 10.1158/2159-8290.CD-18-1177.

KOUAL M, TOMKIEWICZ C, CANO-SANCHO G, et al . Environmental chemicals, breast cancer progression and drug resistance[J ] . Environ Health, 2020, 19(1): 117. DOI: 10.1186/s12940-020-00670-2.

JI X W, DING J, XIE X C, et al . Pollution status and human exposure of decabromodiphenyl ether (BDE-209) in China[J ] . ACS Omega, 2017, 2(7): 3333-3348. DOI: 10.1021/acsomega.7b00559.

GUO J Q, MIAO W B, WU C H, et al . Umbilical cord serum PBDE concentrations and child adiposity measures at 7 years[J ] . Ecotoxicol Environ Saf, 2020, 203: 111009. DOI: 10.1016/j.ecoenv.2020.111009.

ZHAO X Z, SHI Z X. Legacy brominated flame retardants in human milk from the general population in Beijing, China: Biomonitoring, temporal trends from 2011 to 2018, and nursing infant's exposure assessment[J]. Chemosphere, 2021, 285: 131533. DOI: 10.1016/j.chemosphere.2021.131533.

HE Y F, PENG L, ZHANG W C, et al . Adipose tissue levels of polybrominated diphenyl ethers and breast cancer risk in Chinese women: a case-control study[J ] . Environ Res, 2018, 167: 160-168. DOI: 10.1016/j.envres.2018.07.009.

BRITO P M, BISCAIA S M P, DE SOUZA T L, et al . Oral exposure to BDE-209 modulates metastatic spread of melanoma in C57BL/6 mice inoculated with B16-F10 cells[J ] . Chemosphere, 2020, 260: 127556. DOI: 10.1016/j.chemosphere.2020.127556.

FENG Y, HU Q L, MENG G, et al . Simulating long-term occupational exposure to decabrominated diphenyl ether using C57BL/6 mice: Biodistribution and pathology[J ] . Chemosphere, 2015, 128: 118-124. DOI: 10.1016/j.chemosphere.2015.01.012.

HWANG K T, KIM J, JUNG J, et al . Impact of breast cancer subtypes on prognosis of women with operable invasive breast cancer: a population-based study using SEER database[J ] . Clin Cancer Res, 2019, 25(6): 1970-1979. DOI: 10.1158/1078-0432.CCR-18-2782.

YIN L, DUAN J J, BIAN X W, et al . Triple-negative breast cancer molecular subtyping and treatment progress[J ] . Breast Cancer Res, 2020, 22(1): 1-13. DOI: 10.1186/s13058-020-01296-5.

PIEROZAN P, JERNEREN F, KARLSSON O. Perfluorooctanoic acid (PFOA) exposure promotes proliferation, migration and invasion potential in human breast epithelial cells[J]. Arch Toxicol, 2018, 92(5): 1729-1739. DOI: 10.1007/s00204-018-2181-4.

KOUAL M, CANO-SANCHO G, BATS A S, et al . Associations between persistent organic pollutants andrisk of breast cancer metastasis[J ] . Environ Int, 2019, 132: 105028. DOI: 10.1016/j.envint.2019.105028.

SAKAI G, HIRAO-SUXUKI M, KOGA T, et al . Perfluorooctanoic acid (PFOA) as a stimulator of estrogen receptor-negative breast cancer MDA-MB-231 cell aggressiveness: Evidence for involvement of fatty acid 2-hydroxylase (FA2H) in the stimu lated cell migration[J ] . J Toxicol Sci. 2022;47(4): 159-168. doi: 10.2131/jts.47.159.

BENOIT L, KOUAL M, TOMKIEWICZ C, et al . Impact of mixtures of persistent organic pollutants on breast cancer aggressiveness[J ] . Environ Int, 2022, 170: 107615. DOI: 10.1016/j.envint.2022.107615.

KANAYA N, BERNAL L, CHANG G, et al . Molecular mechanisms of polybrominated diphenyl ethers (BDE-47, BDE-100, and BDE-153) in human breast cancer cells and patient-derived xenografts[J ] . Toxicol Sci, 2019, 169(2): 380-398. DOI: 10.1093/toxsci/kfz054.

LI X Y, LIU J H, ZHOU G Q, et al . BDE-209 and DBDPE induce male reproductive toxicity through telomere-related cell senescence and apoptosis in SD rat[J ] . Environ Int, 2021, 146: 106307. DOI: 10.1016/j.envint.2020.106307.

LI Z H, LIU X Y, WANG N, et al . Effects of decabrominated diphenyl ether (PBDE-209) in regulation of growth and apoptosis of breast, ovarian, and cervical cancer cells[J ] . Environ Health Perspect, 2012, 120(4): 541-546. DOI: 10.1289/ehp.1104051.

SHAN A Q, LENG L, LI J, et al . TCDD-induced antag onism of MEHP-mediated migration and invasion partly involves aryl hydrocarbon receptor in MCF 7 breast cancer cells[J ] . J Hazard Mater, 2020, 398: 122869. DOI: 10.1016/j.jhazmat.2020.122869..

LIU S J, LI S T, DU Y G. Polychlorinated biphenyls (PCBs) enhance metastatic properties of breast cancer cells by activating rho-associated kinase (ROCK)[J]. PLoS One, 2010, 5(6): e11272. DOI: 10.1371/journal.pone.0011272.

YU T J, LIU Y Y, LI X G, et al . PDSS1-mediated activation of CAMK2A-STAT3 signaling promotes metastasis in triple-negative breast cancer[J ] .Cancer Res, 2021, 81(21): 5491-5505. DOI: 10.1158/0008-5472.CAN-21-0747.

CAVALCANTE R S, ISHIKAWA U, SILVA E S, et al . STAT3/NF-κB signalling disruption in M2 tumour-associated macrophages is a major target of PLGA nanocarriers/PD-L1 antibody immunomodulatory therapy in breast cancer[J ] . Br J Pharmacol, 2021, 178(11): 2284-2304. DOI: 10.1111/bph.15373.

YANG C C, YU H C, CHEN R, et al . CXCL1 stimulates migration and invasion in ER - negative breast cancer cells via activation of the ERK/MMP2/9 signaling axis[J ] . Int J Oncol, 2019, 55(3): 684-696. DOI: 10.3892/ijo.2019.4840..

DIMRI S, MALHOTRA R, SHET T, et al . Noncanonical pS727 post translational modification dictates major STAT3 activation and downstream functions in breast cancer[J ] . Exp Cell Res, 2020, 396(2): 112313. DOI: 10.1016/j.yexcr.2020.112313.

KOIKE E, YANAGISAWA R, TAKIGAMI H, et al . Penta- and octa-bromodiphenyl ethers promote proinflammatory protein expression in human bronchial epithelial cells in vitro [J ] . Toxicol Vitro, 2014, 28(2): 327-333. DOI: 10.1016/j.tiv.2013.10.014..

KOZLOVA E V, DENYS M E, BENEDUM J, et al . Developmental exposure to indoor flame retardants and hypothalamic molecular signatures: sex-dependent reprogramming of lipid homeostasis[J ] . Front Endocrinol, 2022, 13: 997304. DOI: 10.3389/fendo.2022.997304.

ZHANG Y N, MAO P, LI G Y, et al . Delineation of 3D dose-time-toxicity in human pulmonary epithelial Beas-2B cells induced by decabromodiphenyl ether (BDE209)[J ] . Environ Pollut, 2018, 243(Pt A): 661-669. DOI: 10.1016/j.envpol.2018.09.047.

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