Department of Ophthalmology, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi, P.R. China.
Department of Histology and Embryology, Medical College, Nanchang University, Nanchang 330006, Jiangxi, P.R. China.
Aging (Albany NY). 2021 Mar 3;13(6):8320-8334. doi: 10.18632/aging.202642.
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. 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 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 mice via inhibiting the inflammatory mediators. ZD plays an important role in the process of colon cancers of mice. Celecoxib attenuates ZD-induced colon tumorigenesis in mice by inhibiting the inflammatory mediators. Our novel finding would provide potential prevention of colorectal tumor-induced by ZD.
越来越多的证据表明，膳食锌缺乏（ZD）会增加各种癌症的风险，包括食管癌和胃癌。然而，ZD 在结肠癌发生中的作用尚不清楚，相关机制仍需进一步研究。本研究采用广泛用于模拟人类肠道肿瘤自发过程的 ApcMin/+ 小鼠构建 ZD 小鼠模型。采用实时 PCR 和酶联免疫吸附试验（ELISA）检测 COX-2、TNF-α、CCL、CXCL 和 IL 趋化因子家族等炎症介质。此外，采用免疫组织化学法检测结肠中 cyclin D1、PCNA 和 COX-2 的免疫反应性。我们发现，锌缺乏可促进 ApcMin/+ 小鼠的结肠癌发生。其机制涉及炎症介质的上调：COX-2、TNF-α、CCL、CXCL 和 IL 趋化因子家族。选择性 COX-2 抑制剂塞来昔布的给药通过抑制炎症介质，降低了 ApcMin/+ 小鼠的结肠癌发生。ZD 在 ApcMin/+ 小鼠结肠癌发生过程中起重要作用。塞来昔布通过抑制炎症介质，减轻 ZD 诱导的 ApcMin/+ 小鼠结肠癌发生。我们的新发现为 ZD 诱导的结直肠肿瘤的潜在预防提供了依据。
