The role of mitochondrial regulation in macrophage polarization by Ganoderma lucidum polysaccharide for the treatment of colitis-associated colorectal cancer.

Colorectal cancer (CRC) is a common malignant tumor of the digestive tract. Ganoderma lucidum polysaccharide (GLP) has shown significant potential in regulating macrophage polarization and treating CRC. However, the role of mitochondrial regulation in GLP-mediated macrophage polarization in azoxymethane/dextran sulfate sodium (AOM/DSS)-induced colitis-associated CRC remains unclear. Therefore, we performed cellular and animal experiments to explore how GLP influences mitochondrial dynamics and function, macrophage polarization, and exerts its therapeutic effect against AOM/DSS-induced colitis-associated CRC. The results showed that Mdivi-1 attenuated GLP-induced changes in mitochondrial dynamics and function, further reduced the M1/M2 macrophage ratio. In vivo experiments confirmed that GLP modulates mitochondrial function, promotes M1 macrophage polarization, and thereby inhibits CRC progression without significant side effects. This study provides new insights into the role of mitochondrial modulation in GLP-mediated macrophage polarization and suggests a potential therapeutic avenue for colitis-associated CRC treatment.