Oroxylin A may promote cell apoptosis and inhibit epithelial-mesenchymal transition in endometrial cancer, associated with the ERβ/PI3K/AKT pathway.

Endometrial cancer (EC) is a prevalent gynecological cancer worldwide, often associated with poor prognosis after recurrence or metastasis. Oroxylin A (OA) is an active flavonoid compound with a strong anti-tumor function. However, the effects of OA on EC remain unknown. In this study, we planned to investigate the anti-EC effects of OA and explore its mechanisms. Five cell lines were used for in vitro experiments, and female BALB/c nude mice were applied for xenograft experiments. The cytotoxicity and experimental concentration of OA were detected by CCK-8. Wound healing, transwell, and colony formation assays were used to evaluate the anti-metastatic and anti-proliferative activities of OA on EC cells. TUNEL assay and flow cytometry were applied for the evaluation of apoptosis. Network pharmacology was used to explore potential targets, and molecular dynamics simulations and dockings were applied for the quantification of binding energy, and stability of OA. RT-qPCR, WB, and immunofluorescence were applied for the detection of localization and expression of correlated markers. The results showed that OA notably inhibited the proliferation, migration, and invasion of Ishikawa cells. Meanwhile, in vivo Ishikawa xenograft assays demonstrated that OA notably inhibited growth and promoted apoptosis of EC. Mechanistically, after treatment with OA, the expressions of Cleaved Caspase-3, BAX, E-cadherin, and ERβ were increased, while the expressions of Bcl-2, Vimentin, N-cadherin, MMP2, MMP9, PI3K and phospho-AKT (Ser473) were decreased. Therefore, OA may exhibit significant anti-EC effects by regulating the ERβ/PI3K/AKT pathway to promote apoptosis and inhibit epithelial-mesenchymal transition (EMT).