Zhao YH, Chen J, Gong T, Ge HY, Li M. Icariin inhibits tumor-associated neutrophil recruitment via the CXCL8-CXCR2 axis and restrains pro-metastatic programs in colorectal cancer. World J Gastroenterol 2026; 32(11): 113325 [DOI: 10.3748/wjg.v32.i11.113325]
Corresponding Author of This Article
Min Li, PhD, Department of Oncology, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, No. 157 Daming Road, Nanjing 210022, Jiangsu Province, China. limin_2024@163.com
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Oncology
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Basic Study
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Mar 21, 2026 (publication date) through Mar 27, 2026
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Publication Name
World Journal of Gastroenterology
ISSN
1007-9327
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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA
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Zhao YH, Chen J, Gong T, Ge HY, Li M. Icariin inhibits tumor-associated neutrophil recruitment via the CXCL8-CXCR2 axis and restrains pro-metastatic programs in colorectal cancer. World J Gastroenterol 2026; 32(11): 113325 [DOI: 10.3748/wjg.v32.i11.113325]
World J Gastroenterol. Mar 21, 2026; 32(11): 113325 Published online Mar 21, 2026. doi: 10.3748/wjg.v32.i11.113325
Icariin inhibits tumor-associated neutrophil recruitment via the CXCL8-CXCR2 axis and restrains pro-metastatic programs in colorectal cancer
Yan-Hua Zhao, Juan Chen, Tao Gong, Hai-Yan Ge, Min Li
Yan-Hua Zhao, Juan Chen, Tao Gong, Hai-Yan Ge, Min Li, Department of Oncology, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing 210022, Jiangsu Province, China
Author contributions: Zhao YH designed the research study; Zhao YH and Chen J performed the research; Zhao YH, Gong T, Ge HY, and Li M conducted experiments and analyzed the data; all authors contributed to editorial changes in the manuscript, read and approved the final manuscript.
Institutional animal care and use committee statement: All animal-related procedures were approved by the Institutional Animal Care, Ethics, and Use Committees of Hunan Evidence-Based Biotechnology Co., Ltd., No. NJ2303048.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement: Data are available from the corresponding author upon reasonable request.
Corresponding author: Min Li, PhD, Department of Oncology, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, No. 157 Daming Road, Nanjing 210022, Jiangsu Province, China. limin_2024@163.com
Received: September 23, 2025 Revised: November 16, 2025 Accepted: January 8, 2026 Published online: March 21, 2026 Processing time: 174 Days and 0.9 Hours
Core Tip
Core Tip: This study elucidates a novel mechanism by which the natural compound icariin (ICA) combats colorectal cancer. We demonstrate that ICA upregulates the tumor suppressor SMAD4, thereby inhibiting the production of C-X-C motif chemokine ligand 8 (CXCL8) and other C-X-C motif chemokine receptor 2 (CXCR2)-associated chemokines. This action predominantly limits the recruitment of tumor-associated neutrophils (TANs) via the CXCL8-CXCR2 axis. Notably, ICA not only reduces neutrophil infiltration but also reprograms TANs toward an antitumor N1 phenotype. By disrupting this SMAD4-CXCL8-CXCR2-TAN axis, ICA effectively restrains epithelial-mesenchymal transition and other pro-metastatic processes, positioning it as a promising therapeutic candidate with a distinct immunomodulatory strategy against colorectal cancer progression.
