Chelerythrine: a novel candidate for targeting miR-21/PTEN/PI3K/AKT in nasopharyngeal carcinoma

作者：Wenqing Zhang, Jie Liu, H H Chen, Lan He, Xianwen Wang, Yingchun He, Jingying Fan · 发表于：Journal of Translational Medicine · 年份：2026 · DOI：10.1186/s12967-026-08635-8 · 研究领域：Berberine and alkaloids research、PI3K/AKT/mTOR signaling in cancer、MicroRNA in disease regulation

BACKGROUND: Nasopharyngeal carcinoma (NPC) is characterized by high metastatic potential and therapeutic resistance, necessitating the development of novel and safe therapeutic strategies. Hyperactivation of the PI3K/AKT signaling pathway, often driven by the oncogenic microRNA-21 (miR-21) and the subsequent suppression of PTEN, plays a key role in NPC progression. Chelerythrine (CHE), a natural plant-derived alkaloid, exhibits potent anti-tumor activities; however, its precise regulatory mechanisms and translational potential in NPC remain elusive. METHODS: Network pharmacology was employed to predict the core downstream cascades of CHE against NPC. In vitro, CCK-8, real-time cellular analysis (RTCA), flow cytometry, wound healing, and Transwell assays were utilized to evaluate the specific cytotoxicity and anti-malignant effects of CHE in normal nasopharyngeal epithelial cells (NP69) and NPC cells (5-8 F and 6-10B). RT-qPCR was used to quantify the expression of primary (pri-miR-21), precursor (pre-miR-21), and mature miR-21. In vivo, a BALB/c nude mouse xenograft model was established to systematically assess the tumor-suppressive efficacy and macroscopic/histological biosafety of CHE. Furthermore, definitive rescue experiments were conducted using a specific PI3K activator and lentivirus-mediated miR-21 modification cell lines. RESULTS: Network pharmacology highlighted the PI3K/AKT pathway as the key effector cascade of CHE. Functionally, CHE exhibited a highly favorable ...