Introduction: Esophageal cancer(EC) is a significant clinical challenge due to its aggressiveness and poor prognosis. CD47, a transmembrane protein, inhibits macrophage phagocytosis and is linked to tumor advancement and poor outcomes. The interaction between curcumin(CUR) and CD47 and its effects on EC need further studies. Methods: This study identified common target genes of CUR and EC through network pharmacology, and then found core genes via protein-protein interaction (PPI) analysis. in vitro experiments were conducted to investigate the effects of CUR on cell proliferation, apoptosis, and migration, and to explore the underlying mechanisms. in vivo xenograft experiments were also carried out to evaluate the effects and mechanisms of CUR on tumor growth. Results: CD47 was highly expressed in EC, and CUR shared ten common target genes with EC. Enrichment analysis and PPI network supported PTGS2 and BAX as core genes. in vitro, CUR could inhibit the proliferation and migration of CD47-overexpressing EC cells and induce apoptosis. In the xenograft model, CUR could inhibit tumor growth (p = 0.0144). The mechanism of CUR may be related to multiple components of the MAPK signaling pathway, especially ERK1/2 and its phosphorylation. Additionally, CUR treatment reduced the COX-2 expression level. Immunohistochemistry showed that both BAX and Bcl-2 proteins were upregulated, but the upregulation of BAX protein was significantly more pronounced than that of Bcl-2. Discussion: Our study has confirmed that CUR inhibits CD47-overexpressing esophageal cancer cells. This mechanism may be achieved by blocking ERK1/2 and its phosphorylation, reducing COX2 levels, and enhancing BAX protein expression Conclusion: This study highlights CUR's potential in treating EC, particularly in CD47 overexpression cases. These results clarify the molecular interactions and provide a basis for future research on CUR-based therapies targeting EC progression pathways.
Kang et al. (Tue,) studied this question.