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首页> 外文期刊>Toxicology: An International Journal Concerned with the Effects of Chemicals on Living Systems >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
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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

机译：苯并[a]芘-7,8-diol-9,10-环氧化抑制了通过抑制FAK / SRC / PI3K / AKT途径来调节MMP2的人外向性滋养板HTR-8 / SVNEO细胞的迁移和侵袭

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Moderate invasion of trophoblasts into the endometrium is crucial for successful pregnancy. Benzo[a]pyrene-7,8-dio1-9,10-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 mu M 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 mu M BPDE. The protein and mRNA levels of FAR, 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.
机译：中等孕期侵袭到子宫内膜是成功怀孕的至关重要。苯并[a]芘-7,8-dio1-9,10-环氧化（bpde）是苯并[a]芘的致癌代谢物，导致各种疾病。我们调查了BPDE对滋生素HTR-8 / SVNEO细胞迁移和侵袭的影响。暴露于0.25-1.0μmBDE的细胞迁移和侵袭显着抑制了24小时。此外，在用0.5-1.0μmbde处理的HTR-8 / Svneo细胞温育后，人脐静脉内皮细胞（HUVEC）的管形成也显着降低。随着BPDE浓度的增加，蛋白质和mRNA水平，SRC，PI3K，P-PI3K，AKT，P-AKT，内皮一氧化氮合酶（ENOS）及其活性和基质金属蛋白2（MMP2）显着降低。 SC79的存在，AKT的活化剂，部分衰减了BPDE对迁移和侵袭的抑制作用，证实AKT途径的参与。因此，BPDE通过抑制FAK，SRC和PI3K的表达，抑制人滋养管HTR-8 / SVNEO细胞的迁移和侵袭，从而降低调节PI3K / AKT信号通路。本研究揭示了多环芳烃抑制迁移和孕产妇侵袭的机制，并提高了对妊娠早期胚胎植入对胚胎植入的不利影响的实验理解。

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