Study on the anticancer function and mechanism of cathelicidin-DM in liver cancer.

BACKGROUND

Previous studies have shown that bioactive molecules secreted by toad skin possess anticancer properties. Cathelicidin-DM (C-DM) is a bioactive peptide secreted by toad skin, but its effects on tumor cells and the underlying molecular mechanisms remain unknown.

METHODS

The impact of varying amphibian peptides on the viability of various tumor cells was determined by CCK-8. The influence of C-DM on liver cancer (LC) cell function was investigated using colony formation, flow cytometry, and Transwell. The anti-tumor activity of C-DM was evaluated by xenograft models. RNA-seq was done to confirm differentially expressed genes (DEGs), which were subject to GSEA. Cellular experiments were performed to verify the molecular regulatory mechanism of C-DM in LC.

RESULTS

C-DM (100 μg/mL) had a significant repressive impact on the proliferation, migration, invasion, and cell cycle progression of HepG2 and Hep3B cells, and facilitated apoptosis. In vivo experiments validated the anti-tumor impact of C-DM, while its toxicity was low. DEG DHRS3 was enriched in the JAK-STAT pathway. Overexpression of DHRS3 fostered the malignant phenotype of LC cells and activated the JAK-STAT pathway. However, the addition of C-DM weakened the oncogenic properties of DHRS3 and repressed the JAK-STAT pathway.

CONCLUSION

C-DM exerted an anti-LC effect by downregulating DHRS3 and mediating the JAK-STAT pathway, indicating that C-DM may be a promising candidate drug for LC treatment.