Journal
TOXICOLOGY
Volume 453, Issue -, Pages -Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.tox.2021.152734
Keywords
MEHP; Neuroblastoma; Estrogen receptor alpha; Cell proliferation; Cell invasion
Categories
Funding
- National Natural Science Foundation of China [81972996]
- Science and Technology Project of the Education Department of Jilin Province [JJKH20201076KJ]
- Department of Finance of Jilin Province [JLSWSRCZX2020-090]
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The study revealed that MEHP promotes proliferation, migration, and invasion of neuroblastoma cells through ER alpha by upregulating the expression levels of PCNA, MMP-2, and MMP-9, while downregulating TIMP-2.
Estrogen receptors are involved in regulating the proliferation and invasion process of neuroblastoma. As a kind of estrogen-like environmental endocrine disruptors (EEDs), whether mono-2-ethylhexyl phthalate (MEHP) can affect the proliferation and invasion of neuroblastoma cells via ERs is unknown. The present study aimed to explore the role of ER alpha in MEHP-induced proliferation, migration, and invasion of SH-SY5Y cells. SH-SY5Y cells were cultured in DMEM with 10 % FBS. Wild-type SH-SY5Y cells and ER alpha-knockdown SH-SY5Y cells were treated with MEHP (0, 10, 50, and 250 mu M) for 12 h and 24 h. The viability of SH-SY5Y cells was detected with a CCK8 kit and cell cycle was measured by flow cytometry. Cell migration was measured using a scratch assay, and cell invasion was tested using a Transwell migration assay. The expression levels of proliferating cell nuclear antigen (PCNA), matrix metalloproteinase 2 (MMP-2), matrix metalloproteinase 9 (MMP-9), tissue inhibitor of matrix metalloproteinase 2 (TIMP-2), ER alpha, and ER beta were detected with real-time qPCR and western blotting. MEHP promoted the proliferation of SH-SY5Y cells. The results also showed that MEHP significantly increased the relative migration distance of wild-type SH-SY5Y cells. Conversely, MEHP treatment did not increase the relative migration distance of ER alpha-knockdown SH-SY5Y cells, suggesting that MEHP promotes the migration of neuroblastoma through ER alpha. Similarly, MEHP significantly increased the relative number of invaded wild-type SH-SY5Y cells, while the MEHP-induced invasion effect was significantly decreased in ER alpha-knockdown SH-SY5Y cells. Moreover, the expression levels of PCNA, MMP-2, MMP-9, and ER alpha cells were upregulated by MEHP in wild-type SH-SY5Y, and the expression level of its tissue inhibitor TIMP-2 was downregulated. In contrast, the expression of PCNA, MMP-2, MMP-9, and ER alpha was significantly downregulated in ER alpha-knockdown SH-SY5Y cells, while the expression of TIMP-2 was significantly upregulated. In conclusion, MEHP can upregulate PCNA, MMP-2, and MMP-9, and downregulate TIMP-2, further promoting proliferation, migration, and invasion of neuroblastoma through ER alpha.
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