4.7 Article

AC1Q3QWB inhibits colorectal cancer progression by modulating the immune response and balancing the structure of the intestinal microbiota

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INTERNATIONAL IMMUNOPHARMACOLOGY
卷 116, 期 -, 页码 -

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ELSEVIER
DOI: 10.1016/j.intimp.2023.109768

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AOM; DSS model; Colitis -associated colon cancer; Immune cells; Microbiota

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AC1Q3QWB (AQB) exhibits potent antitumor activity against colorectal cancer in vivo, possibly by modulating the immune system and altering the intestinal microbiota.
AC1Q3QWB enhances CD8 + T cell response and triggers accumulation of Tregs and B cells.Background: Colorectal cancer (CRC) is a common malignancy with high mortality and few effective therapeutic measures. Gut microbiota dysbiosis and chronic inflammation might contribute to the development of CRC. The present study aimed to explore the effect of AC1Q3QWB (AQB) on colon carcinogenesis in vivo.Methods: A mouse colon cancer model was constructed by intraperitoneal injection of 10 mg/kg of Azoxy-methane (AOM) and 2 % dextran sodium sulfate (DSS) in drinking water. Mice were randomly assigned to four groups: normal control (NC), AOM/DSS (model control, MC), DMSO + AOM/DSS (DMSO), and AQB + AOM/DSS (AQB). Mice in the AQB group were treated with an intraperitoneal injection of AQB (50 mg/kg) after successful modeling. Then, the disease activity index (DAI) of colitis was analyzed. Colon tissues were collected for hematoxylin-eosin, immunohistochemistry, and microscopic and histological evaluation. Stool samples were collected for microbiota analysis by 16S rRNA sequencing. Blood samples were analyzed by flow cytometry to investigate the inflammatory response.Results: In AOM/DSS-induced CRC mouse model, AQB treatment dramatically reduced the number and size of colon tumors. AQB treatment enhances CD8++T cell response and triggers the accumulation of CD4++CD25++Foxp3++ Regulatory T cells (Tregs) and B cells. AQB regulated the structure and composition of the gut microbiota, which decreased the Firmicutes/Bacteroidetes ratio at the phylum level and increased the abundance of probiotics.Conclusions: AQB has potent antitumor activity against colorectal cancer in vivo by a mechanism that might involve modulation of the immune system and alteration of the intestinal microbiota.

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