Modified Lichong decoction intervenes in colorectal cancer by modulating the intestinal flora and the Wnt/β-catenin signaling pathway

J Cancer Res Clin Oncol. 2024 May 6;150(5):234. doi: 10.1007/s00432-024-05763-w.

Abstract

Background: The pathogenesis and treatment of colorectal cancer (CRC) continue to be areas of ongoing research, especially the benefits of traditional Chinese medicine (TCM) in slowing the progression of CRC. This study was conducted to investigate the effectiveness and mechanism of action of modified Lichong decoction (MLCD) in inhibiting CRC progression.

Methods: We established CRC animal models using azoxymethane/dextran sodium sulfate (AOM/DSS) and administered high, medium, or low doses of MLCD or mesalazine (MS) for 9 weeks to observe MLCD alleviation of CRC. The optimal MLCD dose group was then subjected to metagenomic and RNA sequencing (RNA-seq) to explore the differentially abundant flora and genes in the control, model and MLCD groups. Finally, the mechanism of action was verified using WB, qRT‒PCR, immunohistochemistry and TUNEL staining.

Results: MLCD inhibited the progression of CRC, and the optimal effect was observed at high doses. MLCD regulated the structure and function of the intestinal flora by decreasing the abundance of harmful bacteria and increasing that of beneficial bacteria. The differentially expressed genes were mainly associated with the Wnt/β-catenin pathway and the cell cycle. Molecular biology analysis indicated that MLCD suppressed the Wnt/β-catenin pathway and the epithelial-mesenchymal transition (EMT), inhibited abnormal cell proliferation and promoted intestinal epithelial cell apoptosis.

Conclusion: MLCD mitigated the abnormal growth of intestinal epithelial cells and promoted apoptosis, thereby inhibiting the progression of CRC. This inhibition was accomplished by modifying the intestinal microbiota and disrupting the Wnt/β-catenin pathway and the EMT. Therefore, MLCD could serve as a potential component of TCM prescriptions for CRC treatment.

Keywords: Cell cycle; Colorectal cancer; Epithelial–mesenchymal transition; Intestinal flora; Lichong decoction; Wnt/β-catenin.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Cell Proliferation / drug effects
  • Colorectal Neoplasms* / drug therapy
  • Colorectal Neoplasms* / metabolism
  • Colorectal Neoplasms* / pathology
  • Dextran Sulfate
  • Disease Models, Animal
  • Drugs, Chinese Herbal* / pharmacology
  • Epithelial-Mesenchymal Transition / drug effects
  • Gastrointestinal Microbiome* / drug effects
  • Humans
  • Male
  • Mice
  • Wnt Signaling Pathway* / drug effects
  • beta Catenin / metabolism

Substances

  • Drugs, Chinese Herbal
  • Dextran Sulfate
  • beta Catenin