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Benzo[a]pyrene-7,8-diol-9,10-epoxide suppresses the migration and invasion of human extravillous trophoblast HTR-8/SVneo cells by down-regulating MMP2 through inhibition of FAK/SRC/PI3K/AKT pathway.

Authors :
Wang, Rong
Wang, Weiping
Ao, Lin
Wang, Zhi
Hao, Xianglin
Zhang, Huidong
Source :
Toxicology. Jul2017, Vol. 386, p72-83. 12p.
Publication Year :
2017

Abstract

Moderate invasion of trophoblasts into the endometrium is crucial for successful pregnancy. Benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE) is a carcinogenic metabolite of benzo[a]pyrene which causes various diseases. We investigated the effects of BPDE on migration and invasion of trophoblast HTR-8/SVneo cells. Migration and invasion of cells exposed to 0.25-1.0 μM BPDE for 24 h were significantly inhibited. Moreover, tube formation of human umbilical vein endothelial cell (HUVEC) was also significantly reduced after incubation with HTR-8/SVneo cells treated with 0.5-1.0 μM BPDE. The protein and mRNA levels of FAK, SRC, PI3K, p -PI3K, AKT, p -AKT, endothelial nitric oxide synthase (eNOS) and its activity, and matrix metalloproteinase 2 (MMP2) significantly decreased with increasing BPDE concentration. The presence of SC79, activator of AKT, partially attenuates the inhibition effect of BPDE on migration and invasion, confirming the involvement of AKT pathway. Thus, BPDE suppresses migration and invasion of human trophoblast HTR-8/SVneo cells by inhibiting the expression of FAK, SRC and PI3K, consequently down-regulating PI3K/AKT signaling pathway. This study reveals the mechanism of Polycyclic aromatic hydrocarbons-inhibited migration and invasion of trophoblast, and enhanced our experimental understanding of the adverse effects of PAHs on embryo implantation in early pregnancy. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
0300483X
Volume :
386
Database :
Academic Search Index
Journal :
Toxicology
Publication Type :
Academic Journal
Accession number :
124420571
Full Text :
https://doi.org/10.1016/j.tox.2017.05.008