Celecoxib alleviates zinc deficiency-promoted colon tumorigenesis through suppressing inflammation

Abstract

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. Apc min/+ 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 Apc min/+ 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 Apc min/+ mice via inhibiting the inflammatory mediators. ZD plays an important role in the process of colon cancers of Apc min/+ mice. Celecoxib attenuates ZD-induced colon tumorigenesis in Apc min/+ mice by inhibiting the inflammatory mediators. Our novel finding would provide potential prevention of colorectal tumor-induced by ZD.

Zinc in Cognitive Impairment and Aging

“…Use of the zinc chelator, N , N , N′ , N′ tetrakis(2-pyridinylmethyl)-1,2-ethanediamine reduces the LPS-induced increase in the formation of NLRP3-level IL-1β, while reducing neuronal death [ 41 ]. In addition, nutritional zinc deficiency can increase the levels of the inflammatory factors, CCL2, CXCL2, CXCL5, IL-1, IL-6, and TNF-α in the serum and in colonic mucosa, accelerating the development of colonic tumors [ 42 ]. In animal experiments, zinc supplementation of 120 mg/kg improved the growth performance of Pekin ducks; it reduced intestinal damage and increased intestinal enzyme activity.…”

miR-137 represses migration and cell motility by targeting COX-2 in non-small cell lung cancer

“…Bothe specific and non-specific inhibitors of COX-2, such as nonsteroidal anti-inflammatory drugs (NSAIDs), can induce apoptosis of gastric cancer, colorectal cancer, and pancreatic cancer cells ( 34 ). A study on esophageal cancer showed celecoxib could inhibit the expression of COX-2, down regulate the expression of PGE, inhibit the proliferation of esophageal cancer cells, and improve the therapeutic effect of chemotherapy and radiotherapy ( 35 ).…”

Chemokines in progression, chemoresistance, diagnosis, and prognosis of colorectal cancer

“…Apart from that, certain trace element deficiencies may cause the cancer to grow. Zinc deficiency, for example, significantly promotes the mRNA and protein levels of CCL2, CXCL2, and CXCL5 in the colonic mucosa and tumorigenesis in the colon (122).…”