Mesalazine Suppresses Colorectal Cancer Liver Metastasis via the HDAC3/Wnt/β-Catenin Axis Through Downregulating Bacteroides fragilis Abundance

Colorectal Cancer (CRC) is characterized by high recurrence and metastasis, resulting in low patient survival. Dysbiosis of intestinal flora increases CRC metastasis risk. Mesalazine, an anti-inflammatory drug with proven antitumor activity, is commonly used to treat CRC in patients with inflammatory bowel disease, but whether it mediates CRC hepatic metastasis by affecting key flora is unknown. An animal model of CRC liver metastasis was established by injecting HCT116 cells into the spleens of mice and treated with mesalazine. Mouse feces were collected for 16S rRNA Sequencing to analyze the abundance of intestinal flora. In vitro experiments demonstrated that mesalazine inhibited proliferation, migration, and invasion of CRC by modulating Bacteroides fragilis. Rescue experiments validated molecular mechanisms. Mesalazine inhibited CRC hepatic metastasis and reduced the abundance of Bacteroides fragilis in the feces of CRC hepatic metastatic mice by 16S rRNA Sequencing analysis. In vitro experiments showed that mesalazine inhibited proliferation, migration, and invasion of CRC by affecting Bacteroides fragilis, mainly through the histone deacetylase 3 (HDAC3)/Wingless/Int/Beta-catenin (Wnt/β-catenin) axis. The study elucidated the mechanism by which mesalazine inhibited CRC liver metastasis through the HDAC3/Wnt/β-catenin axis by affecting the abundance of Bacteroides fragilis, which provided a new idea for CRC treatment.

Bacteroides fragilis; HDAC3; Wnt/β‐catenin; colorectal cancer; mesalazine.