Swertianin Promotes Anti-Tumor activity by facilitating Macrophage M1 polarization via STING signaling

Area of Science:

• Immunology
• Pharmacology
• Oncology

Background:

• Tumor microenvironment (TME) macrophages often exhibit immunosuppressive M2 phenotypes.
• Repolarizing M2 macrophages to an anti-tumor M1 phenotype is a promising cancer therapy strategy.

Purpose of the Study:

• To elucidate the mechanism of swertiamarin (SWE)-induced M1 macrophage polarization.
• To investigate SWE's anti-tumor effects mediated by macrophage repolarization.

Main Methods:

• Utilized RAW264.7 and primary monocyte-derived macrophages.
• Employed STING and NF-κB (P65) knockout models.
• Assessed M1 polarization markers (e.g., CD86).
• Evaluated tumor growth inhibition in animal models.

Main Results:

• SWE promoted M1 cell formation and increased CD86+ cells in macrophages.
• SWE activated the STING-NF-κB signaling pathway.
• STING or P65 knockout antagonized SWE's effects on M1 polarization.
• SWE inhibited tumor growth and promoted CD86+ cells in vivo, an effect blunted by STING knockout.

Conclusions:

• Swertiamarin activates the STING-NF-κB pathway to promote M1 macrophage polarization.
• This M1 polarization contributes to swertiamarin's anti-tumor activity.
• Targeting the STING-NF-κB pathway with SWE shows therapeutic potential in cancer treatment.