PPARδ Antagonist Inhibited CD47 Expression and Phagocytosis

ABSTRACT Increasing evidence suggests that CD47 is highly expressed in multiple types of cancer, which could bind to SIRPα on macrophage, leading to inhibition of macrophage phagocytosis and promotion of tumor growth. However, the regulatory mechanism of CD47 gene expression is not completely clear. Our results indicated that colon cancer cells treated with GSK0660 drug, which is one of the PPARδ antagonists, significantly reduced CD47 gene and protein expression levels in a time and dose‐dependent manner. CD47 reporter plasmid was constructed and dual‐luciferase analysis was performed. The results suggest that GSK0660 treatment markedly reduced CD47 gene transcriptional activity. Moreover, co‐cultured analysis showed that GSK0660 treatment increased phagocytosis. BALB/C mice implanted with CT‐26 colon cancer cells were treated with GSK0660, and the results showed that GSK0660 significantly inhibited tumor growth. Moreover, the combination of CD47 monoclonal antibody with GSK0660 drug significantly inhibited tumor growth compared to GSK0660 or CD47 antibody treatment alone. These findings suggest that GSK0660 synergized with CD47 antibody to enhance antitumor immunotherapy.