Colorectal cancer (CRC) is one of the major malignancies in humans. This study was designed to evaluate the effects of fucoidan on gut flora and tumor prevention in 1,2-dimethylhydrazine-induced colorectal carcinogenesis in rats. We found that dietary fucoidan treatment decreased the tumor incidence and mean tumor weight and increased cell apoptosis. Fucoidan treatment decreased the expression of β-catenin C-Myc, CyclinD1 and Survivin, while the Hippo pathway was activated with increased phosphorylation levels of mammalian sterile 20-like kinase 1 and 2, large tumor suppressor 1 and 2, and Yes-associated protein. Compared with the model group, the levels of interleukin (IL)-17 and IL-23 were decreased, but the levels of interferon-γ, IL-4 and IL-10 were increased, in the fucoidan group. Fucoidan treatment increased natural killer cells in peripheral blood and the proportion of CD4+ T cells. Immunofluorescence detection of colorectal tumor tissues showed decreased expression of Foxp3 and up-regulated expression of CD68 in the fucoidan group. Moreover, fucoidan treatment decreased the levels of diamine oxidase and lipopolysaccharides and up-regulated the levels of tight junction proteins. 16S rDNA high-throughput sequencing revealed that fucoidan treatment decreased the abundance of Prevotella and increased the abundance of Alloprevotella. Fucoidan increased the levels of butyric acid and valeric acid compared to the model group. This study provides experimental evidence that dietary fucoidan may prevent colorectal tumorigenesis by regulating gut microecology and body immunity. Meanwhile, fucoidan activated the Hippo pathway and down-regulated the β-catenin pathway to induce tumor cell apoptosis and suppress tumor growth.
Keywords: 1,2-Dimethylhydrazine; Colorectal tumor; Fucoidan; Gut flora; Intestinal mucosal barrier function; Short-chain fatty acids.
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