Qi Dan, Lu Jingyuan, Fu Ziyi, Lv Shanshan, Hou Lili
Department of Traditional Chinese Medicine, Nanjing Maternity and Child Health Care Hospital, Women's Hospital of Nanjing Medical University, Nanjing, China.
Department of Radiological Intervention, Nanjing Maternity and Child Health Care Hospital, Women's Hospital of Nanjing Medical University, Nanjing, China.
Front Pharmacol. 2022 Apr 8;13:804400. doi: 10.3389/fphar.2022.804400. eCollection 2022.
Recurrent spontaneous abortion (RSA) is a kind of pathological pregnancy, and abnormal function of trophoblast cells may be related to a variety of pregnancy complications including RSA. Psoralen is an effective ingredient extracted from (L.) Medik. with multiple bioactivities mainly including anti-osteoporotic, anti-tumor, anti-inflammatory, and estrogen-like effects. However, the exact role of psoralen on trophoblast invasiveness has not been investigated thus far. In the present study, the effects of psoralen on the proliferation, migration, and invasion abilities of HTR-8/SVneo cells were evaluated by the CCK-8 and Transwell assays. The expression patterns of nuclear factor κB (NF-κB)/p65 and metalloproteinases (MMP)-2 and MMP-9 were characterized by further experiments including real-time quantitative polymerase chain reaction and Western blot. Indirect immunofluorescence was applied to track the NF-κB p65 translocation. Herein, we found that cell viability and invasive ability were promoted by psoralen in a concentration-dependent manner. Psoralen concentration-dependently enhanced both MMP-2 and MMP-9 expression and their activity of HTR-8/SVneo cells. Additionally, we observed accelerated nuclear accumulation and enhanced nuclear translocation of p65 in the presence of psoralen. Furthermore, invasiveness enhancement of psoralen on HTR-8/SVneo cells was partly eliminated by a NF-κB pathway inhibitor. Thus, our findings suggest that psoralen may serve as a potential repurpose drug candidate that can be used to induce migration and invasion of trophoblast cells through strengthening the NF-κB pathway.
复发性自然流产（RSA）是一种病理性妊娠，滋养层细胞功能异常可能与包括RSA在内的多种妊娠并发症有关。补骨脂素是从补骨脂中提取的一种有效成分，具有多种生物活性，主要包括抗骨质疏松、抗肿瘤、抗炎和雌激素样作用。然而，补骨脂素对滋养层细胞侵袭性的确切作用迄今尚未得到研究。在本研究中，通过CCK-8和Transwell试验评估了补骨脂素对HTR-8/SVneo细胞增殖、迁移和侵袭能力的影响。通过实时定量聚合酶链反应和蛋白质免疫印迹等进一步实验，对核因子κB（NF-κB）/p65以及金属蛋白酶（MMP）-2和MMP-9的表达模式进行了表征。应用间接免疫荧光法追踪NF-κB p65的易位。在此，我们发现补骨脂素以浓度依赖的方式促进细胞活力和侵袭能力。补骨脂素浓度依赖性地增强了HTR-8/SVneo细胞中MMP-2和MMP-9的表达及其活性。此外，我们观察到在补骨脂素存在的情况下，p65的核内积累加速且核易位增强。此外，NF-κB通路抑制剂部分消除了补骨脂素对HTR-8/SVneo细胞侵袭性的增强作用。因此，我们的研究结果表明，补骨脂素可能是一种潜在的可重新利用的药物候选物，可通过加强NF-κB通路来诱导滋养层细胞的迁移和侵袭。
