The mechanism of luteolin suppressing pancreatic cancer (PC) via cyclin B1 (CCNB1)-mediated signalling.

Pancreatic cancer is a highly aggressive malignancy with a poor prognosis, often diagnosed at advanced stages. Current treatments are limited, underscoring the need for effective therapies. Recent studies suggest that luteolin exhibits significant anti-tumor activity, yet its mechanisms in pancreatic cancer remain poorly understood. This study explored the anti-tumor mechanism of luteolin in pancreatic cancer (PC), focusing on its regulation of cyclin B1 (CCNB1)-mediated cell cycle progression. PANC-1 and SW1990 cell lines were used for assays of cell proliferation, migration, and invasion, and flow cytometry was used to assess cell cycle distribution and apoptosis. The efficacy of luteolin was further evaluated in patient-derived organoids (PDOs) and a mouse xenograft model. To identify molecular targets, we employed network pharmacology and transcriptomic sequencing, followed by experimental validation using Western blot, molecular docking, and surface plasmon resonance (SPR) assays to confirm luteolin's interaction with CCNB1 and its effects on downstream signaling pathways. Luteolin exhibited a dose-dependent inhibitory effect on pancreatic cancer cell proliferation, migration, and invasion. It induced G2/M cell cycle arrest and apoptosis, with significant suppression of PDO growth. In vivo, luteolin effectively inhibited subcutaneous tumor growth in a xenograft mouse model without causing systemic toxicity or organ damage. Network pharmacology and transcriptomic analyses identified CCNB1 as a pivotal target, and experimental validation confirmed luteolin's direct binding to CCNB1. This interaction disrupted the CCNB1/cyclin-dependent kinase 1 (CDK1) complex, leading to cell cycle arrest and reduced tumor progression. Luteolin suppresses pancreatic cancer growth by targeting CCNB1-mediated cell cycle regulation, inducing G2/M arrest, and promoting apoptosis. This highlights its potential as a therapeutic agent in pancreatic cancer treatment.