Dual Targeting of Cell Growth and Phagocytosis by Erianin for Human Colorectal Cancer

Abstract

Objective

To investigate the effect of erianin on tumor growth and immune response in human colorectal cancer cells (CRC).

Methods

The effect of erianin on tumor growth was determined by CCK8 and colony formation assay. Western blotting was used to evaluate the expression levels of relevant proteins and qRT-PCR was used to evaluate the mRNA level of the relevant gene. The transcriptional activity of β-catenin was determined by dual-luciferase reporter assay. Cellular thermal shift assay was used to quantify drug–target interactions. The cell surface CD47 was assessed by flow cytometry. The enrichment of H3K27 acetyl marks on CD47 promoter was evaluated by chromatin immunoprecipitation assay. Phagocytosis assay was used to determine the phagocytic activity of macrophage. In vivo role of erianin was studied on xenograft models.

Results

We found that erianin significantly decreased cell survival, colony formation, induced cell cycle arrest, and led to cell apoptosis in SW480 and HCT116 cells. Mechanism analysis demonstrated that erianin inhibited the nuclear translocation and transcriptional activity of β-catenin, which might result from erianin-β-catenin interaction. In addition, the downstream gene expressions, such as c-Myc and cyclin D1, was decreased. More interestingly, erianin decreased the expression of CD47 by regulating H3K27 acetyl marks enrichment on CD47 promoter. Consequently, macrophage-mediated phagocytosis was increased. Our in vivo experiments further confirmed the inhibitory effect of erianin on tumor growth.

Conclusion

In summary, erianin could inhibit CRC cells growth and promoted phagocytosis, which suggested erianin as a potential therapeutic strategy for CRC patients.

Keywords:

• erianin
• colorectal cancer
• β-catenin
• CD47
• macrophage

Author Contributions

All authors contributed towards data analysis, drafting and critically revising the paper, gave final approval of the version to be published, and agreed to be accountable for all aspects of the work.

Disclosure

The authors declare no conflicts of interest in this work.