Department of Preventive Medicine and Environmental Health, University of Kentucky, 121 Washington Avenue, Lexington, KY 40536, USA.
Toxicol Appl Pharmacol. 2011 Oct 15;256(2):114-21. doi: 10.1016/j.taap.2011.07.016. Epub 2011 Aug 11.
Long term exposure to arsenic can increase incidence of human cancers, such as skin, lung, and colon rectum. The mechanism of arsenic induced carcinogenesis is still unclear. It is generally believed that reactive oxygen species (ROS) may play an important role in this process. In the present study, we investigate the possible linkage between ROS, β-catenin and arsenic induced transformation and tumorigenesis in human colorectal adenocarcinoma cell line, DLD1 cells. Our results show that arsenic was able to activate p47(phox) and p67(phox), two key proteins for activation of NADPH oxidase. Arsenic was also able to generate ROS in DLD1 cells. Arsenic increased β-catenin expression level and its promoter activity. ROS played a major role in arsenic-induced β-catenin activation. Treatment of DLD1 cells by arsenic enhanced both transformation and tumorigenesis of these cells. The tumor volumes of arsenic treated group were much larger than those without arsenic treatment. Addition of either superoxide dismutase (SOD) or catalase reduced arsenic induced cell transformation and tumor formation. The results indicate that ROS are involved in arsenic induced cell transformation and tumor formation possible through Wnt/β-catenin pathway in human colorectal adenocarcinoma cell line DLD1 cells.
长期接触砷会增加人类癌症的发病率，如皮肤癌、肺癌和结肠癌。砷诱导致癌的机制尚不清楚。一般认为活性氧（ROS）可能在此过程中发挥重要作用。在本研究中，我们研究了 ROS、β-连环蛋白和砷诱导的转化和肿瘤发生之间的可能联系在人结直肠腺癌细胞系 DLD1 细胞中。我们的结果表明，砷能够激活 NADPH 氧化酶的两个关键蛋白 p47(phox)和 p67(phox)。砷还能够在 DLD1 细胞中产生 ROS。砷增加了β-连环蛋白的表达水平及其启动子活性。ROS 在砷诱导的β-连环蛋白激活中起主要作用。用砷处理 DLD1 细胞增强了这些细胞的转化和肿瘤发生。用砷处理组的肿瘤体积明显大于未用砷处理组。添加超氧化物歧化酶（SOD）或过氧化氢酶可减少砷诱导的细胞转化和肿瘤形成。结果表明，ROS 通过 Wnt/β-连环蛋白通路参与砷诱导的细胞转化和肿瘤形成，可能在人结直肠腺癌细胞系 DLD1 细胞中。
