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Promotion of breast cancer cells MDA-MB-231 invasion by di(2-ethylhexyl)phthalate through matrix metalloproteinase-2/-9 overexpression.
- Source :
-
Environmental science and pollution research international [Environ Sci Pollut Res Int] 2016 May; Vol. 23 (10), pp. 9742-9. Date of Electronic Publication: 2016 Feb 06. - Publication Year :
- 2016
-
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.
- Subjects :
- Breast Neoplasms enzymology
Breast Neoplasms pathology
Cell Line, Tumor
Enzyme Induction drug effects
Estrogen Receptor alpha metabolism
Female
Gene Expression drug effects
Gene Expression Regulation, Neoplastic drug effects
Humans
Matrix Metalloproteinase 2 genetics
Matrix Metalloproteinase 9 genetics
NF-kappa B metabolism
Neoplasm Invasiveness
Signal Transduction drug effects
Up-Regulation
Breast Neoplasms chemically induced
Diethylhexyl Phthalate toxicity
Endocrine Disruptors toxicity
Environmental Pollutants toxicity
Matrix Metalloproteinase 2 metabolism
Matrix Metalloproteinase 9 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1614-7499
- Volume :
- 23
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Environmental science and pollution research international
- Publication Type :
- Academic Journal
- Accession number :
- 26850096
- Full Text :
- https://doi.org/10.1007/s11356-016-6158-7