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Promotion of breast cancer cells MDA-MB-231 invasion by di(2-ethylhexyl)phthalate through matrix metalloproteinase-2/-9 overexpression

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Abstract

Di(2-ethylhexyl)phthalate (DEHP) is an estrogenic chemical that is widely used in polyvinyl products. We aimed to determine the mechanisms behind the effects of DEHP on ERα-negative breast cancer cells MDA-MB-231 invasion and matrix metalloproteinases-2/-9 (MMP-2/-9) up-regulation in this study. Transwell assay indicated that DEHP exposure (>50 μg/ml) significantly enhanced the invasion ability of MDA-MB-231 cells. Quantitative real-time PCR (qPCR) and western blotting revealed that MMP-2/-9 is overexpressed in mRNA and protein levels after DEHP treatment. Gelatin zymography consistently demonstrated that DEHP exposure also enhances the activity of MMP-2/-9. Immunofluorescence assay showed that DEHP could accelerate NF-kappaB (NF-κB) subunits-p65 translocation into the nucleus, which is confirmed by western blotting assay, suggesting that the ratio of nuclear/cytosolic level of p65 was significantly increased. Furthermore, the invasion and MMP-2/-9 overexpression of MDA-MB-231 cells after DEHP-treated were reversed by the NF-κB chemical inhibitor JSH-23 via drug inhibition assay. This study suggested that DEHP could promote ERα-negative breast cancer cells MDA-MB-231 invasion through activating NF-κB and MMP-2/-9 overexpression.

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Acknowledgments

Project supported by National Natural Science Foundation of China (Grant No. 81302304, 81402139)

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    Authors and Affiliations

    1. Nanjing Maternal and Child Health Institute, Nanjing Maternal and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing, 210004, China

      Shuya Zhang, Ziyi Fu, Zhilei Zhang & Pengfei Xu

    2. Department of Biotechnology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, 210029, China

      Shuya Zhang, Zhilei Zhang & Xin Cao

    3. Department of Reproductive Health, Nanjing Maternity and Child Health Care Hospital Affiliated of Nanjing Medical University, Nanjing, 210004, China

      Jiehua Ma

    4. Department of Gynecologic Endocrinology, Nanjing Maternal and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing, 210004, China

      Jian Cao

    5. The First Clinical Medical College of Nanjing Medical University, Nanjing, 210029, China

      Lei Huang & Wenqu Li

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    1. Shuya Zhang
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    3. Ziyi Fu
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    Correspondence to Pengfei Xu or Xin Cao.

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    Responsible editor: Philippe Garrigues

    Shuya Zhang and Jiehua Ma contributed equally to this work.

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    Zhang, S., Ma, J., Fu, Z. et al. Promotion of breast cancer cells MDA-MB-231 invasion by di(2-ethylhexyl)phthalate through matrix metalloproteinase-2/-9 overexpression. Environ Sci Pollut Res 23, 9742–9749 (2016). https://doi.org/10.1007/s11356-016-6158-7

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