砷化物通过炎症相关信号通路对肿瘤调控的研究进展
Research progress on mechanism of inflammatory signaling pathway-driven cancer induced by arsenide
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摘要:
肿瘤已经成为严重危害人类生存和社会发展的重大疾病，是当今世界共同面临的公共卫生问题之一。研究表明，大约20%的肿瘤与慢性炎症密切相关，使得环境致癌物通过炎症反应导致肿瘤发生发展的机制研究越来越受到学者的关注。砷化物作为一种环境毒物，可以产生急、慢性毒性作用，使得细胞中的炎症细胞因子异常表达，改变细胞微环境，最终导致肿瘤的发生发展。有趣的是，砷类中药及其制剂却能够通过调控炎症信号通路，抑制肿瘤的生长，在治疗白血病等肿瘤研究中显现出良好的应用前景。因此，砷化物具有致癌又治癌两种截然不同的生物学效应。研究表明，砷化物主要通过调控核转录因子B(NF-κB)和活化蛋白-1(AP-1)等转录因子的数量和活性，影响环氧合酶-2(COX-2)和肿瘤坏死因子-α(TNF-α)等炎症细胞因子的表达，导致细胞凋亡和黏附等生物学行为的改变，从而调控肿瘤的发生发展。为了进一步阐释砷化物通过不同炎症相关信号通路对肿瘤进行调控的分子机制，本文就砷化物在炎症微环境致肿瘤消长过程中的调控作用进行了论述。
Abstract: Cancer has become one of the most serious diseases which severely harm the health of human beings and the development of human society, and it has been a serious public health problem that the world has to face. Studies show that 20% cancers are related closely with chronic inflammation, and more and more scholars pay attention to the mechanism of environmental carcinogen on tumorigenesis through inflammatory reaction. Arsenide as an environmental carcinogen can generate both acute and chronic toxicity, induce the overexpression of inflammatory cytokines, change cellular microenvironment, and result in tumorigenesis. Interestingly, Chinese traditional arsenic medicine can inhibit tumor growth through regulating inflammatory signaling pathways, and have a good application prospect in tumor therapy, such as leukemia treatment. Therefore, arsenide has two totally different biological effects, carcinogenic and anticarcinogenic. Research indicates that arsenide can regulate the number and activity of transcript factors such as nuclear factor-kappa B (NF-κB) and activator protein-1 (AP-1), influence the expressions of inflammatory cytokines such as cyclooxygenase-2 (COX-2) and tumor necrosis factor-α (TNF-α), lead to changes in bioactivity like cell apoptosis and adhesion, and then regulate tumorigenesis development. In order to further illustrate the molecular mechanism of how arsenide regulates tumorigenesis through different inflammatory signaling pathways, the review summarized evidence linking inflammatory microenvironment to tumor growth and shrinkage regulated by arsenide.
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