Luteolin improves precancerous conditions of the gastric mucosa by binding STAT3 and inhibiting LCN2 expression
Inhibition of malignant transformation from the precancerous stage has important clinical value for the prevention of gastric cancer. Here, we report a strategy to inhibit precancerous gastric conditions by Luteolin (Lut). Lut treatment resulted in remarkable resistance to oxyntic atrophy, spasmolytic polypeptide-expressing metaplasia (SPEM), and gastric mucosal injury in tamoxifen (TAM)-treated mice, chenodeoxycholic acid-treated rats, and human organoids. Mechanism study suggested that LCN2 expression was upregulated in the SPEM mucosa and downregulated after Lut treatment. LCN2 blocking suppressed TAM-induced oxyntic atrophy and metaplasia and partially counteracted the effect of Lut. Quantitative chemoproteomics identified that Lut bound to STAT3 and inhibited its phosphorylation. Functional experiments using STAT3 inhibitors and epithelial cell-specific <i>Stat3</i> deficient mice showed that STAT3 inhibition and deletion attenuated the beneficial effects of Lut. Our data supported that Lut might be a therapeutic candidate for the treatment of gastric mucosal injury by binding to STAT3 and thereby inhibiting the STAT3/LCN2 axis.
Authors
- Yueqing Gong (ORCID: https://orcid.org/0000-0001-6741-0475)
- Shigang Ding (ORCID: https://orcid.org/0000-0002-0831-0965)
- Chao Ma (ORCID: https://orcid.org/0000-0001-6728-4114)
- Ying Xiong (ORCID: https://orcid.org/0000-0001-7412-1727)
- Yuanfei Zhou (ORCID: https://orcid.org/0009-0005-8261-195X)
- Xinyu Hao (ORCID: https://orcid.org/0000-0002-0634-3333)
- Shouli Yuan
- Weichao Xu (ORCID: https://orcid.org/0000-0001-5232-5462)
- Weiwei Fu (ORCID: https://orcid.org/0000-0003-3543-854X)
- Jing Ning (ORCID: https://orcid.org/0000-0002-5454-3188)
- Xiaohuan Guo (ORCID: https://orcid.org/0000-0001-5152-3010)
- Yanfei Lang (ORCID: https://orcid.org/0009-0007-3097-0605)
- Jing Zhang (ORCID: https://orcid.org/0000-0002-6313-5741)
- Yangang Wang (ORCID: https://orcid.org/0000-0002-1325-9252)
- Xiurui Han (ORCID: https://orcid.org/0000-0001-9304-6902)
- Meng Qiao (ORCID: https://orcid.org/0000-0003-1186-0439)
- Rongli Cui
Institutions
- Beijing University of Chinese Medicine (CN)
- Peking University (CN)
- National Clinical Research Center for Digestive Diseases (CN)
- Hospital of Hebei Province (CN)
- Jining Traditional Chinese Medicine Hospital (CN)
- Beijing National Laboratory for Molecular Sciences (CN)
- Hebei University of Chinese Medicine (CN)
- Peking University Third Hospital (CN)
- Center for Life Sciences (CN)
- Tsinghua University (CN)
Publication Details
- Journal
- International Journal of Biological Sciences
- Published
- 2025-05-07
- DOI
- https://doi.org/10.7150/ijbs.111636
- Citations
- 8
- Primary Topic
- Helicobacter pylori-related gastroenterology studies
- Type
- article
- Field-Weighted Citation Impact
- 16.05
Funders
- National Natural Science Foundation of China
- Beijing National Laboratory for Molecular Sciences