Kaempferol's potential in targeting IL-17-mediated inflammatory pathways for colorectal cancer treatment

Area of Science:

• Oncology
• Immunology
• Pharmacology

Background:

• Colorectal cancer (CRC) presents limited therapeutic options for advanced stages.
• Interleukin-17 (IL-17) signaling is implicated in promoting tumor progression and immune evasion in CRC.
• The role of kaempferol, a natural flavonol, in modulating IL-17 pathways in CRC remains largely unexplored.

Purpose of the Study:

• To investigate the therapeutic potential of kaempferol in modulating IL-17 signaling pathways in colorectal cancer.
• To evaluate the efficacy of kaempferol monotherapy and its combination with PD-L1 inhibitors in a preclinical CRC model.
• To elucidate the molecular mechanisms underlying kaempferol's anti-tumor effects in CRC.

Main Methods:

• Utilized an immunocompetent MC38 xenograft model for evaluating kaempferol efficacy.
• Assessed tumor growth, immune cell infiltration, cytokine profiles, and signaling pathway activation.
• Employed techniques including immunohistochemistry, ELISA, flow cytometry, and Western blotting.

Main Results:

• Kaempferol demonstrated dose-dependent suppression of tumor growth and synergistic effects with PD-L1 inhibitors.
• Kaempferol enhanced CD4+ and CD8+ T cell infiltration while reducing IL-17A+ γδ T cells and increasing IFN-γ+ γδ T cells.
• Kaempferol downregulated key inflammatory mediators (IL-6, TNF-α, IL-17A) and inhibited STAT3/NF-κB pathway activation.

Conclusions:

• Kaempferol effectively inhibits colorectal cancer progression by targeting IL-17-mediated inflammation and bolstering anti-tumor immunity.
• Combination therapy with PD-L1 inhibitors potentiates kaempferol's anti-cancer effects.
• Kaempferol represents a potential novel therapeutic agent for colorectal cancer treatment.