Gastrointestinal cancerCCL20 mediates the anti-tumor effect of vitamin D3 in p38MAPK/NF-κB signaling in colitis-associated carcinogenesisXin, Yua; Wang, Hongjuana; Wang, Yanana; Xu, Weihuaa; Teng, Guoxinb; Han, Fuyanc; Guo, JianqiangaAuthor Information Departments of aGastroenterology bPathology cClinical Laboratory, The Second Hospital of Shandong University, Jinan, Shandong, PR China Received 22 October 2019 Accepted 24 January 2020 Correspondence to Jianqiang Guo, MD, The Second Hospital of Shandong University, Jinan 250033, Shandong, PR China, Tel: +17660080388; e-mail: [email protected] European Journal of Cancer Prevention: January 2021 - Volume 30 - Issue 1 - p 76-83 doi: 10.1097/CEJ.0000000000000582 Buy Metrics Abstract Vitamin D3 is beneficial in ameliorating or preventing inflammation and carcinogenesis. CCL20 is a potential therapeutic target in carcinogenesis, which mediates the protective effect of vitamin D or vitamin D analogue in autoimmune and cancer diseases. Here we aim to evaluate whether vitamin D3 plays a protective role in colitis-associated colorectal cancer (CAC) by affecting CCL20 and the molecular mechanism. Administration of azoxymethane (AOM) followed with dextran sulfate sodium (DSS) was used to simulate CAC in mouse. After 5-day DSS treatment, vitamin D3 supplementation was for 9 weeks at 60 IU/g/w. We found that dietary vitamin D3 significantly reduced the tumor number and tumor burden in mouse. In-vivo and -vitro, vitamin D3 reduced the levels of CCL20, phospho-p38 MAPK (p-p38) and phospho-NF-κB p65 (p-p65), and the transcriptional activity of NF-κB. Further studies showed that CCL20 mediated the inhibition of vitamin D3 in p38MAPK-mediated NF-κB signaling in vitro. Taken together, vitamin D3 effectively suppressed colonic carcinogenesis in AOM-DSS mouse model. Downregulation of CCL20 may contribute to the preventive effect of vitamin D3 on NF-κB activity. It may merit further clinical investigation as a therapeutic agent against CAC in humans. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.