College of Pharmaceutical Sciences & Chinese Medicine, Southwest University, Chongqing, China.
Chongqing Key Laboratory of New Drug Screening from Traditional Chinese Medicine, Chongqing, China.
Int J Biol Sci. 2021 Jun 11;17(10):2449-2460. doi: 10.7150/ijbs.60167. eCollection 2021.
Previously the potential therapeutic action of ferulic acid, ligustrazine and tetrahydropalmatine (FLT) are discovered with unclear mechanism in rat autograft endometriosis. However, the effect of FLT on endometrial cells and allograft endometriosis is still unclear. This study is designed to elucidate the influence of FLT on epithelial-mesenchymal transformation in allograft endometriosis and endometrium cells. , fluorescent xenogeneic endometriosis model was established. , invasion and metastasis were analyzed after treating FLT. Epithelial-mesenchymal transformation and Wnt/β-catenin pathway were inspected and . Activator or inhibitor of Wnt/β-catenin signaling was performed to inspect mechanism of epithelial-mesenchymal transformation. , FLT not only decreased fluorescent intensity and volume of ectopic lesion, but also ameliorated pathological morphology. E and PROG levels in serum were reduced by FLT. In endometrial cells, FLT significantly inhibited the invasion and metastasis. Meantime, epithelial-mesenchymal transformation was reversed, accompanied by suppression of Wnt/β-catenin pathway. In-depth study, activation of Wnt/β-catenin pathway lead to promotion of epithelial-mesenchymal transformation, which was reversed by FLT. FLT prevented fluorescent allograft endometriosis and endometrium cells, which was related to suppress epithelial-mesenchymal transformation through inactivating Wnt/β-catenin pathway. The findings disclose molecular mechanism of epithelial-mesenchymal transformation in endometriosis by FLT, and contribute to further application.
先前已经发现阿魏酸、川芎嗪和延胡索乙素(FLT)在大鼠自体子宫内膜异位症中有潜在的治疗作用,但 FLT 对子宫内膜细胞和同种异体子宫内膜异位症的影响尚不清楚。本研究旨在阐明 FLT 对同种异体子宫内膜异位症和子宫内膜细胞上皮间质转化的影响。 建立荧光异种子宫内膜异位症模型。 用 FLT 处理后分析侵袭和转移。 检查上皮间质转化和 Wnt/β-catenin 通路,并进行 Wnt/β-catenin 信号转导的激活剂或抑制剂实验,以检查上皮间质转化的机制。 结果表明,FLT 不仅降低了异位病变的荧光强度和体积,还改善了病理形态。血清中 E 和 PROG 水平也被 FLT 降低。在子宫内膜细胞中,FLT 显著抑制了侵袭和转移。同时,上皮间质转化被逆转,伴随着 Wnt/β-catenin 通路的抑制。深入研究表明,Wnt/β-catenin 通路的激活导致上皮间质转化的促进,而 FLT 可逆转这一过程。FLT 预防荧光同种异体子宫内膜异位症和子宫内膜细胞,这与通过抑制 Wnt/β-catenin 通路来抑制上皮间质转化有关。这些发现揭示了 FLT 通过抑制 Wnt/β-catenin 通路抑制上皮间质转化从而抑制子宫内膜异位症的分子机制,为进一步的应用提供了依据。