BDE-209暴露通过STAT3信号通路促进三阴性乳腺癌细胞的迁移

谢尚富; 卢林明; 江孟晓; 王琪; 支慧

doi:10.16016/j.2097-0927.202302085

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BDE-209暴露通过STAT3信号通路促进三阴性乳腺癌细胞的迁移

基础医学 | 更新时间：2026-01-09

- BDE-209暴露通过STAT3信号通路促进三阴性乳腺癌细胞的迁移
- Decarbromodiphenyl ether (BDE-209) exposure promotes migration of triple-negative breast cancer cells through STAT3 signaling pathway
- 陆军军医大学学报 2023年45卷第17期页码：1838-1845
- 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：
  
  [支慧，E-mail : zhi_hui01@hotmail.comZHI Hui, E-mail: zhi_hui01@hotmail.com
- 基金信息：
- DOI：10.16016/j.2097-0927.202302085
  中图分类号： R730.23;R737.9;R994.6
- 收稿：2023-02-15，
  
  修回：2023-05-31，
  
  纸质出版：2023-09-15
- 稿件说明：
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谢尚富, 卢林明, 江孟晓, 等. BDE-209暴露通过STAT3信号通路促进三阴性乳腺癌细胞的迁移[J]. 陆军军医大学学报, 2023,45(17):1838-1845.

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.
谢尚富, 卢林明, 江孟晓, 等. BDE-209暴露通过STAT3信号通路促进三阴性乳腺癌细胞的迁移[J]. 陆军军医大学学报, 2023,45(17):1838-1845. DOI： 10.16016/j.2097-0927.202302085.

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

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