Research Paper Volume 13, Issue 6 pp 8320—8334
Celecoxib alleviates zinc deficiency-promoted colon tumorigenesis through suppressing inflammation
- 1 Department of Ophthalmology, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi, P.R. China
- 2 Department of Histology and Embryology, Medical College, Nanchang University, Nanchang 330006, Jiangxi, P.R. China
- 3 Queen Mary School, Medical College, Nanchang University, Nanchang 330006, Jiangxi, P.R. China
Received: August 8, 2020 Accepted: December 9, 2020 Published: March 3, 2021https://doi.org/10.18632/aging.202642
How to Cite
Copyright: © 2021 Yin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Accumulating evidence has shown that dietary zinc deficiency (ZD) increases the risk of various cancers including esophageal and gastric cancer. However, the role of ZD in colon tumorigenesis is unknown and the related mechanisms need to be investigated. Apcmin/+ mice, widely used to mimic the spontaneous process of human intestinal tumor, were used to construct a ZD mice model in this study. Inflammatory mediators such as COX-2, TNF-α, CCL, CXCL, and IL chemokines families were evaluated using real-time PCR and Enzyme-linked immunosorbent assay (ELISA). Besides, the immunoreactivities of cyclin D1, PCNA, and COX-2 in the colon were detected by immunohistochemistry. We found that zinc deficiency could promote colon tumorigenesis in Apcmin/+ mice. The mechanisms are involved in the upregulation of inflammatory mediators: COX-2, TNF-α, CCL, CXCL, and IL chemokines families. Administration of celecoxib, a selective COX-2 inhibitor, decreased colon tumorigenesis in Apcmin/+ mice via inhibiting the inflammatory mediators. ZD plays an important role in the process of colon cancers of Apcmin/+ mice. Celecoxib attenuates ZD-induced colon tumorigenesis in Apcmin/+ mice by inhibiting the inflammatory mediators. Our novel finding would provide potential prevention of colorectal tumor-induced by ZD.
Akt: protein kinase B; Apcmin/+: Apc, adenomatous polyposis coli, Min, Multiple intestinal neoplasia; CCL: C-C motif chemokines; COX-2: cyclooxygenase-2; CRC: Colorectal cancer; CSCs: cancer stem cells; CXCL: C-X-C motif chemokines; CXCR: C-X-C motif chemokine receptors; ELISA: Enzyme-linked immunosorbent assay; EMT: epithelial-mesenchymal transition; ENA78: epithelial neutrophil activating peptide 78; ERK1/2: extracellular regulated protein kinases; GSK3β: Glycogen synthase kinase3 beta; HCC: hepatocellular carcinoma cell; IHC: immunohistochemistry; NSAIDs: nonsteroidal anti-inflammatory drug; NMBA: N-nitrosomethylbenzylamine; PCNA: Proliferating Cell Nuclear Antigen; PD-1: programmed cell death protein 1; PI3K: phosphoinositide 3-kinase; TNF-α: Tumor Necrosis Factor alpha; IL: Interleukin; ZD: zinc deficiency; ZS: zinc sufficiency.