Oncotarget

Research Papers:

Propoxur enhances MMP-2 expression and the corresponding invasion of human breast cancer cells via the ERK/Nrf2 signaling pathway

Yunxiang Shi, Daizhi An, Yiping Liu, Qiong Feng, Xu Fang, Guilan Pan and Qiang Wang _

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Oncotarget. 2017; 8:87107-87123. https://doi.org/10.18632/oncotarget.19081

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Abstract

Yunxiang Shi1,*, Daizhi An1,*, Yiping Liu2,*, Qiong Feng1, Xu Fang1, Guilan Pan3 and Qiang Wang1

1Center of Hygiene Assessment and Research, Institute of Disease Control and Prevention, Academy of Military Medical Sciences, Beijing 100071, China

2Beijing Municipal Public Security Hospital, Beijing Municipal Public Security Bureau, Beijing 100006, China

3Department of Physiology, BaoTou Medical College, Inner Mongolia University of Science and Technology, Baotou 014040, China

*These authors contributed equally to this work

Correspondence to:

Qiang Wang, email: [email protected]

Keywords: propoxur, matrix metalloproteinase, nuclear factor E2-related factor 2, extracellular signal-regulated kinase 1/2

Received: December 21, 2016     Accepted: June 20, 2017     Published: July 07, 2017

ABSTRACT

Propoxur is considered a prime etiological suspect of increasing tumor incidence, but the role is still undefined. In this study, two human breast cancer cells lines, MCF-7 and MDA-MB-231 cells, were used as cell models. Cells were respectively treated with 0, 0.01, 1, or 100 μM propoxur. PD98059, a MEK inhibitor, was administered to block the ERK/MAPK pathway. Migration and reactive oxygen species were measured by wound healing and Transwell assays, and flow cytometry. Protein expression and subcellular location were detected by western blotting and immunofluorescence staining, respectively. Results showed that propoxur treatment enhanced cell migration and invasion in a dose-dependent manner, while MMP-2 expression, but not MMP-9, was significantly increased in two cell lines. Meanwhile, the treatment increased intracellular reactive oxygen species, Nrf2 expression and nuclear translocation, and ERK1/2 phosphorylation. Inversely, inhibition of ERK1/2 activation with PD98059 significantly attenuated propoxur-induced Nrf2 expression and nuclear translocation. Moreover, PD98059 suppressed propoxur-induced cell migration and invasion, and MMP-2 overexpression. Collectively, these results indicate that propoxur can trigger reactive oxygen species overproduction, further promoting breast cancer cell migration and invasion by regulating the ERK/Nrf2 signaling pathways.


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