三氯生暴露对三阴性乳腺癌细胞侵袭能力的影响

doi:10.3969/j.issn.1674-8115.2026.04.004

上海交通大学学报（医学版） ›› 2026, Vol. 46 ›› Issue (4): 442-450.doi: 10.3969/j.issn.1674-8115.2026.04.004

• 论著 · 基础研究 • 上一篇

三氯生暴露对三阴性乳腺癌细胞侵袭能力的影响

童有华, 郭思楠, 聂宇, 高雅宣, 刘世艳, 张浩浩, 侯英豪, 支慧()

皖南医学院基础医学院病理解剖学教研室，芜湖 241002

收稿日期:2025-06-17 接受日期:2025-11-27 出版日期:2026-04-28 发布日期:2026-04-28
通讯作者: 支慧，副教授，博士；电子信箱：Zhi_hui01@hotmail.com。
作者简介:第一联系人：为共同第一作者（co-first authors）。
基金资助:
国家自然科学基金(21906122);安徽省高校自然科学研究项目(2024AH051899);皖南医学院国家级大学生创新训练计划项目(202310368008);肿瘤免疫病理学教育部重点实验室开放课题(2024jsz1010)

Effects of triclosan exposure on the invasion ability of triple-negative breast cancer cells

Tong Youhua, Guo Sinan, Nie Yu, Gao Yaxuan, Liu Shiyan, Zhang Haohao, Hou Yinghao, Zhi Hui()

Department of Pathology, School of Basic Medical Sciences, Wannan Medical College, Wuhu 241002, China

Received:2025-06-17 Accepted:2025-11-27 Online:2026-04-28 Published:2026-04-28
Contact: Zhi Hui, E-mail: Zhi_hui01@hotmail.com.
Supported by:
National Natural Science Foundation of China(21906122);Natural Science Research Project of Anhui Educational Committee(2024AH051899);National Innovation and Entrepreneurship Training Program for Undergraduates of Wannan Medical College(202310368008);Open Project of Key Laboratory of Tumor Immunology and Pathology, Ministry of Education(2024jsz1010)

摘要/Abstract

摘要：

目的·探究三氯生（triclosan，TCS）暴露对三阴性乳腺癌（triple-negative breast cancer，TNBC）进展的影响及其可能的作用机制。方法·采用细胞计数试剂盒8（cell counting kit-8，CCK-8）检测TCS对TNBC细胞MDA-MB-231的半数抑制浓度，以筛选TCS的暴露浓度。分别采用划痕实验、Transwell细胞侵袭实验检测TCS对MDA-MB-231细胞的迁移与侵袭能力的影响。采用实时荧光定量PCR（quantitative real-time PCR，qPCR）检测TCS对MDA-MB-231细胞中miR-21表达的影响，蛋白质印迹法（Western blotting）检测TCS对MDA-MB-231细胞上皮-间质转化（epithelial-mesenchymal transition，EMT）相关蛋白［E-钙黏蛋白（E-cadherin，E-cad）、波形蛋白（vimentin）］的影响。利用免疫组织化学技术与蛋白质印迹法检测TCS暴露对miR-21/STAT3（信号转导和转录活化因子3，signal transducer and activator of transcription 3）信号通路的影响；同时，对MDA-MB-231细胞转染miR-21 mimics，检测TCS暴露对该细胞的迁移与侵袭能力的影响。结果·根据CCK-8实验结果，筛选出TCS的暴露浓度为0.001、0.01、0.1和1 μmol/L。划痕实验与Transwell细胞侵袭实验的结果均显示，0.01、0.1、1 μmol/L TCS暴露均可增强MDA-MB-231细胞的迁移、侵袭能力（均P<0.05）。qPCR的结果表明，0.01、0.1、1 μmol/L TCS暴露后miR-21在TNBC细胞的表达水平均有所下降（均P<0.05）。蛋白质印迹法的结果显示，0.1、1 μmol/L TCS均可下调上皮细胞标志物E-cad的表达，0.01、0.1、1 μmol/L TCS均可上调间叶细胞标志物vimentin的表达（均P<0.05）。免疫组织化学与蛋白质印迹法的结果显示，0.01、0.1、1 μmol/L TCS暴露均可增加STAT3的磷酸化，且呈现剂量依赖效应（均P<0.05）。转染miR-21 mimics上调miR-21的表达后，TCS促进TNBC细胞迁移与侵袭的能力均受到了抑制（均P<0.05）。结论·TCS暴露可通过miR-21/STAT3 信号轴增强TNBC细胞的迁移与侵袭，提示TCS暴露可能对TNBC的进展产生促进效应。

关键词: 三氯生, 三阴性乳腺癌, 侵袭, miRNA-21, 信号转导和转录激活因子3

Abstract:

Objective ·To investigate the effect of triclosan (TCS) exposure on the progression of triple-negative breast cancer (TNBC) and to explore the underlying mechanism. Methods ·Cell counting kit-8 (CCK-8) assay was used to detect the half-maximal inhibitory concentration of TCS in the TNBC cell line MDA-MB-231 to screen the exposure concentrations of TCS. The effects of TCS on the migration and invasion abilities of MDA-MB-231 cells were detected by wound-healing assay and Transwell invasion assays, respectively. The effect of TCS on miR-21 expression in MDA-MB-231 cells was detected by quantitative real-time PCR (qPCR). The effects of TCS on the expression of epithelial-mesenchymal transition (EMT)-related proteins, including E-cadherin (E-cad) and vimentin in MDA-MB-231 cells, were detected by Western blotting. The effect of TCS exposure on the miR-21/signal transducer and activator of transcription 3 (STAT3) signaling pathway were detected by immunohistochemistry and Western blotting. Meanwhile, miR-21 mimics were transfected into MDA-MB-231 cells to examine the effects of TCS exposure on the migration and invasion of the cells. Results ·According to the CCK-8 assay, the exposure concentrations of TCS were screened to be 0.001, 0.01, 0.1, and 1 μmol/L. Wound-healing assay and Transwell invasion assay both showed that exposure to 0.01, 0.1, and 1 μmol/L TCS enhanced the migration and invasion abilities of MDA-MB-231 cells (all P<0.05). qPCR results indicated that the expression level of miR-21 in TNBC cells was decreased after exposure to 0.01, 0.1, and 1 μmol/L TCS (all P<0.05). Western blotting results revealed that 0.1 and 1 μmol/L TCS downregulated the expression of the epithelial marker E-cad, and 0.01, 0.1, and 1 μmol/L TCS upregulated the expression of the mesenchymal marker vimentin (all P<0.05). Immunohistochemistry and Western blotting results demonstrated that exposure to 0.01, 0.1, and 1 μmol/L TCS increased the phosphorylation of STAT3 in a dose-dependent manner (all P<0.05). Upregulation of miR-21 by transfection with miR-21 mimics attenuated the promoting effect of TCS on the migration and invasion of TNBC cells (both P<0.05). Conclusion ·TCS exposure enhances the migration and invasion of TNBC cells via the miR-21/STAT3 signaling axis, suggesting that TCS exposure may exert a promoting effect on the progression of TNBC.

Key words: triclosan (TCS), triple-negative breast cancer (TNBC), invasion, miRNA-21, signal transducer and activator of transcription 3 (STAT3)

中图分类号:

R737.9

童有华, 郭思楠, 聂宇, 高雅宣, 刘世艳, 张浩浩, 侯英豪, 支慧. 三氯生暴露对三阴性乳腺癌细胞侵袭能力的影响[J]. 上海交通大学学报（医学版）, 2026, 46(4): 442-450.

Tong Youhua, Guo Sinan, Nie Yu, Gao Yaxuan, Liu Shiyan, Zhang Haohao, Hou Yinghao, Zhi Hui. Effects of triclosan exposure on the invasion ability of triple-negative breast cancer cells[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2026, 46(4): 442-450.

图/表 7

表 1 qPCR的引物序列

Tab 1 Primer sequences for qPCR

Primer	Forward (5'→3')	Reverse (5'→3')
miR-21	ACACTCCAGCTGGGTAGCTTATCAGACTGA	TGGTGTCGTGGAGTCG
U6	CGATACAGAGAAGATTAGCATGGC	AACGCTTCACGAATTTGCGT

图1 CCK-8法筛选TCS暴露浓度Note： ①P=0.036, ②P=0.014, ③P<0.001, compared with the BC group.

Fig 1 Screening of TCS exposure concentrations by CCK-8 assay

图2 TCS暴露对MDA-MB-231细胞迁移与侵袭能力的影响Note： A. Migration ability of MDA-MB-231 cells treated with different concentrations of TCS by wounding-healing assay (×40). Scale bar=200 μm. B. Quantitative analysis of migration ability of MDA-MB-231 cells in each group. C. Invasion ability of MDA-MB-231 cells treated with different concentrations of TCS by transwell-matrigel assay (×100). Scale bar=50 μm. D. Quantitative analysis of number of invaded cells in each group. ①P=0.022, ②P=0.005, ③P<0.001,④P=0.038, ⑤P=0.002.

Fig 2 Effect of TCS exposure on the migration and invasion abilities of MDA-MB-231 cells

图3 TCS暴露对MDA-MB-231细胞EMT的影响Note： A. Detection of E-cad and Vimentin expression in MDA-MB-231 cells treated with different concentrations of TCS by Western blotting. B/C. Relative expression levels of E-cad (B) and Vimentin (C) in cells treated with different concentrations of TCS. ①P=0.002, ②P=0.001, ③P=0.006, ④P=0.002, ⑤P<0.001.

Fig 3 Effect of TCS exposure on EMT in MDA-MB-231 cells

图4 TCS暴露对STAT3信号通路的影响Note： A. Detection of STAT3, p-STAT3, and MMP9 expression in MDA-MB-231 cells treated with different concentrations of TCS by Western blotting. B‒D. Relative expression levels of STAT3 (B), p-STAT3 (C), and MMP9 (D). ①P=0.005 ②P=0.002, ③P<0.001, ④P=0.008, ⑤P=0.003, ⑥P=0.005. E. Immunohistochemical staining of p-STAT3 in MDA-MB-231 cells (×100). Scale bar=50 μm. F. Migration ability of MDA-MB-231 cells treated with STAT3-IN-1 and TCS by wounding-healing assay (×40). Scale bar=200 μm. G. Quantitative analysis of migration ability of MDA-MB-231 cells in each group. ⑦P=0.005. H. Invasion ability of MDA-MB-231 cells treated with STAT3-IN-1 and TCS by transwell-matrigel assay (×100). Scale bar=50 μm. I. Quantitative analysis of the number of invaded cells in each group. ⑧P=0.007.

Fig 4 Effect of TCS exposure on the STAT3 signaling pathway

图5 TCS暴露对miR-21表达水平的影响Note： A. Relative expression levels of miR-21 in MDA-MB-231 cells exposed to various concentrations of TCS. ①P=0.001,②P=0.003,③P<0.001. B. Correlation analysis between TCS exposure concentration and miR-21 expression level.

Fig 5 Effect of TCS exposure on miR-21 expression levels

图6 过表达miR-21对由TCS诱导的STAT3活化、细胞迁移及侵袭的影响Note： A. Effects of miR-21 on the expression of STAT3 and p-STAT3 in TCS-treated MDA-MB-231 cells. B/C. Relative expression levels of STAT3 (B) and p-STAT3 (C) in TCS-exposed MDA-MB-231 cells. D. Migration ability of MDA-MB-231 cells treated with miR-21 mimics and TCS by wounding-healing assay (×40). Scale bar=200 μm. E. Quantitative analysis of migration ability of MDA-MB-231 cells in each group. F. Invasion ability of MDA-MB-231 cells treated with miR-21 mimics and TCS by transwell-matrigel assay (×100). Scale bar=50 μm. G. Quantitative analysis of the number of invaded cells in each group. ①P=0.001, ②P<0.001, ③P=0.004.

Fig 6 Effect of miR-21 overexpression on TCS-induced STAT3 activation, cell migration, and invasion

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三氯生暴露对三阴性乳腺癌细胞侵袭能力的影响

Effects of triclosan exposure on the invasion ability of triple-negative breast cancer cells

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