Exploring the mechanism of Hua-Zhuo-Jie-Du Formula on colitis-associated colorectal cancer

Hua-Zhuo-Jie-Du Formula (HZJDF), a traditional Chinese medicine formulation, has been clinically proven to be effective in preventing colitis-associated colorectal cancer (CAC). However, the potential therapeutic mechanism of this formulation for CAC remains unclear. This research intends to integrate network pharmacology, transcriptomics and pharmacological experiments to elucidate the mechanism by which HZJDF treats CAC. Initially, we developed a CAC mouse model using the azioximethane dextran sulfate sodium induction method and evaluated the efficacy of different doses of HZJDF in treating CAC. Subsequently, the probable mechanism of HZJDF in treating CAC was predicted using the integration of network pharmacology and transcriptomics. Finally, these prediction findings were further validated by animal and cell experiments. HZJDF dose-dependently alleviated weight loss and shortening of the colon length, increased the survival rate, reduced the DAI score, decreased the occurrence of tumors, and ameliorated the pathological deterioration of the colon tissue of CAC mice. The integration of network pharmacology and transcriptomics revealed that the PI3K AKT signaling pathway may serve as a possible mechanism by which HZJDF exerts its effects against CAC. In vivo experiments demonstrated that HZJDF inhibited the production of Ki67-positive cells in the colon tissues of CAC mice, and reduced the levels of phosphorylated PI3K and AKT proteins.