Long-term inflammatory stimulation is considered one of the most important causes of colorectal cancer. Diphenyleneiodonium (DPI), an NADPH oxidase inhibitor, can inhibit a variety of inflammatory responses. However, the systemic toxicity of DPI limits its clinical application. Whether DPI can inhibit colitis-associated colorectal cancer (CAC) at ultralow concentrations remains unknown./nMethods: CAC was induced by azoxymethane (AOM) injection followed by treatment with dextran sulfate sodium (DSS), and DPI was intraperitoneally injected (i.p.) in the first cycle for 21 days. Colon tissue was collected and analyzed by western blotting. Immune cell infiltration and macrophage polarization were examined by immunohistochemistry, immunofluorescence, or real-time polymerase-chain reaction (PCR). Reactive oxygen species (ROS) production was measured by flow cytometry./nResults: Ultralow dose DPI significantly ameliorated the DSS-induced colitis and attenuated the colon tumorigenesis in the mouse model of AOM/ DSS-induced CAC. Mechanistically, an ultralow dose of DPI inhibited the production of pro-inflammatory cytokines, (tumor necrosis factor (TNF)-α and interleukin (IL)-6), reduced the macrophage infiltration and classical polarization, and induced the ROS generation. These effects were found to be related to the inhibition of the phosphorylation of signal transducer and activator of transcription 3 (STAT3), mitogen-activated protein kinase (MAPK), and nuclear factor kappa B (NF -κB)./nConclusion: The present study revealed that an ultralow dose of DPI, with no significant systemic toxicity involved, may be an effective way to prevent the occurrence and development of CAC.

中文翻译：

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超低剂量的NADPH氧化酶抑制剂联苯二碘铵（DPI）是一种经济有效的治疗剂，用于治疗与结肠炎相关的大肠癌。

长期的炎症刺激被认为是结直肠癌的最重要原因之一。NADPH氧化酶抑制剂联苯二碘铵（DPI）可以抑制多种炎症反应。但是，DPI的全身毒性限制了其临床应用。是否DPI可以在超低浓度遗体unknown./n抑制结肠炎相关结直肠癌（CAC）的方法：通过乙氧基甲烷（AOM）注射诱导诱导CAC，然后用葡聚糖硫酸钠（DSS）处理，并在第一个周期腹膜内注射（ip）DPI，持续21天。收集结肠组织并通过蛋白质印迹分析。通过免疫组织化学，免疫荧光或实时聚合酶链反应（PCR）检查了免疫细胞浸润和巨噬细胞极化。活性氧物质（ROS）的产生通过流式细胞cytometry./n测量结果：在AOM / DSS诱导的CAC小鼠模型中，超低剂量DPI显着改善了DSS诱导的结肠炎并减弱了结肠肿瘤的发生。从机理上讲，超低剂量的DPI抑制促炎细胞因子（肿瘤坏死因子（TNF）-α和白介素（IL）-6）的产生，减少了巨噬细胞的浸润和经典极化，并诱导了ROS的产生。发现这些效应是相关的信号转导和转录因子3（STAT3），促分裂原活化蛋白激酶（MAPK），和核因子κB（NF-κB）./的n活化剂的磷酸化的抑制。结论：本目前的研究表明，超低剂量的DPI，不涉及明显的全身毒性，可能是预防CAC发生和发展的有效方法。