PI3K/AKT/GSK-3β/β-catenin信号通路是子宫内膜异位症发病机制中的诱发因素，其中epithelial to mesenchymal transition (EMT)发挥着关键作用。Parthenolide是一种倍半萜内酯提取物，具有抗炎、镇痛和抗癌特性。因此，我们对Parthenolide在子宫内膜异位组织植入物和细胞系12Z中对EMT的影响进行了研究。我们用24只行手术诱导异位子宫内膜症的雌性大鼠进行了为期4周的parthenolide(2, 4 mg/kg)治疗。用子宫内膜细胞株12Z研究了parthenolide对子宫内膜异位细胞创伤愈合、细胞迁移和侵袭能力的影响。Parthenolide降低了异位内膜组织的total PI3K、PI3K-p85、p-AKT、p/total AKT、p-GSK-3β、p/total GSK-3β 和nβ-catenin的表达，同时增加了E-cadherin的mRNA表达而减少了vimentin的mRNA表达。Parthenolide上调了PTEN的免疫反应活性以及异位组织中的caspase-3、caspase-9、BAX水平，同时降低了Bcl2水平。此外，Parthenolide减少了异位内膜组织植入物的表面积和上皮生长的组织病理得分。我们的发现表明，Parthenolide以剂量依赖的方式抑制了PI3K/AKT/GSK-3β/nβ-catenin级联反应，通过增强PTEN的表达，从而抑制了EMT的发生，表现为上调上皮标记物E-cadherin，减少间质标记物vimentin在子宫内膜异位植入物中的表达，以及逆转了上皮内膜异位细胞系的侵袭和迁移特性。这些发现为治疗子宫内膜异位症提供了有价值的治疗方法。版权所有© 2023。Elsevier Inc.出版。

PI3K/AKT/GSK-3β/β-catenin signaling pathway is a triggering factor for epithelial to mesenchymal transition (EMT) which plays a pivotal role in the pathogenesis of endometriosis. Parthenolide is a sesquiterpene lactone extract, has anti-inflammatory, analgesic and anticancer properties. Hence, we investigated the effect of parthenolide against EMT in the endometrial tissue implants and immortalized epithelial endometriotic cell lines 12Z.Twenty- four female Rats with surgically induced endometriosis were treated with parthenolide (2, 4 mg/kg), for 4 weeks. Endometriotic cell line 12Z was used to identify the effect of parthenolide on the wound healing, cellular migration and invasion properties of endometriotic cells.Parthenolide decreased the endometriotic implant tissue expression of total PI3K, PI3K-p85, p-AKT, p/total AKT, p-GSK-3β, P/total GSK-3β, and nβ-catenin, as well as increased E-cadherin and decreased vimentin mRNA expression. Parthenolide upregulated PTEN immunoreactivity as well as the endometriotic tissue caspase-3, caspase-9, BAX levels while reducing Bcl2 level. Additionally, parthenolide decreased endometriotic tissue implants surface area and histopathological score of the epithelial growth.Our findings showed that parthenolide in a dose dependent manner inhibited PI3K/AKT/GSK-3β/nβ-catenin cascade via enhancement of PTEN with subsequent inhibition of EMT evidenced by elevation of the epithelial marker, E-cadherin, reduction of mesenchymal marker, vimentin, of the endometriotic implants in addition to reversal of invasion and migration properties of epithelial endometriotic cell lines. These findings provide a valuable therapeutic approach for treatment of endometriosis.Copyright © 2023. Published by Elsevier Inc.