Corynoxine suppresses lung adenocarcinoma proliferation and metastasis via inhibiting PI3K/AKT pathway and suppressing Cyclooxygenase-2 expression

作者：Liping Chen, Jing Xing, Jiapei Lv, Sai'nv Si, Huaying Wang, Wanjun Yu · 发表于：Hereditas · 年份：2024 · DOI：10.1186/s41065-024-00343-x · 被引用次数：4 · 研究领域：Alkaloids: synthesis and pharmacology、Magnolia and Illicium research、Berberine and alkaloids research

BACKGROUND: Lung adenocarcinoma (LUAD) is the most common lung cancer subtype, and the prognosis of affected patients is generally poor. The traditional Chinese medicine Uncaria rhychophaylla has been reported to exhibit anti-lung cancer properties. Accordingly, the main bioactive ingredient in Uncaria rhychophaylla, Corynoxine, may hold great value as a treatment for lung cancer. METHODS: The impact of Corynoxine on the viability of LUAD cells was assessed using the Cell Counting Kit-8 (CCK-8) assay. Apoptosis in A549 cells was evaluated via flow cytometry. Migration and invasion capabilities were determined through wound healing and Transwell assays, respectively. The key pathways targeted by Corynoxine in LUAD were identified using a network pharmacology approach. Additionally, Western immunoblotting, quantitative real-time PCR (qRT-PCR), and ELISA assays were conducted to validate the underlying mechanisms. The in vivo anti-tumor efficacy of Corynoxine was assessed in xenograft nude mice. RESULTS: In this study, Corynoxine treatment was found to markedly suppress in vitro LUAD cell proliferative, migratory, and invasive activity. It additionally downregulated Vimentin and promoted E-cadherin upregulation consistent with the disruption of epithelial-mesenchymal transition (EMT) induction while also accelerating apoptotic death. Furthermore, network pharmacology analysis revealed that the PI3K/AKT pathway is a potential target of Corynoxine in LUAD. In vitro assays demonstr...