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

Toxicology
Rong WangHuidong Zhang

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 0.25-1.0μM BPDE for 24h 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 0.5-1.0μM 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 ...Continue Reading

Citations

May 5, 2018·Stroke; a Journal of Cerebral Circulation·Kyeong-A KimOk-Nam Bae
Mar 28, 2018·Journal of Materials Science. Materials in Medicine·Celio J da Costa FernandesWillian F Zambuzzi
Jun 29, 2018·Archives of Gynecology and Obstetrics·Zhifu ZhiLihong Pang
Nov 19, 2020·International Journal of Molecular Sciences·Jin SeokGi Jin Kim
Mar 20, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Yun GaoLiping Peng
Feb 15, 2019·The Science of the Total Environment·Shen XuLizhong Zhu

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