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

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

  • Sci Rep. 2025 Nov 26;15(1):42044. doi: 10.1038/s41598-025-25973-7.
Linjia Peng 1 2 3,  Xiaonan Guo 1 3,  Xinxin Kong 1 3,  Haiting Zhang 1 3,  Yanfeng Liang 1 3,  Qiuli Zhang 1 3,  Zhiguang Ren 1,  Daxiang Cui 4 5
Affiliations

Affiliations

  • 1 The First Afffliated Hospital of Henan University, N. Jinming Ave, Kaifeng, 475004, China.
  • 2 Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
  • 3 Medical and Engineering Cross Research Institute, First affiliated Hospital, Henan University School of Medicine, N. Jinming Ave, Kaifeng, 475004, China.
  • 4 The First Afffliated Hospital of Henan University, N. Jinming Ave, Kaifeng, 475004, China. [email protected].
  • 5 Department of Instrument Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai, 200240, China. [email protected].
PMID: 41298459 DOI: 10.1038/s41598-025-25973-7
Abstract

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.

Keywords

CCNB1; Cell cycle; Luteolin; Pancreatic cancer.

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