Work

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

Year: 2025

Type: article

Abstract: 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. 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. 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. 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. • This study confirmed the anti-tumor activity of cathelicidin-DM on liver cancer cells. • DHRS3 is identified as a key oncogenic driver in liver cancer, promoting malignant phenotypes via activation of the JAK-STAT signaling pathway. • C-DM antagonizes DHRS3-mediated JAK-STAT pathway activation, revealing a novel molecular mechanism for its anti-tumor efficacy.

Source: Genomics

DOI: 10.1016/j.ygeno.2025.111049

Authors: Huang Hu, Jingjing Tai, Ruiyun Zhang, Hong Zhang

Institutions: Jinhua University of Vocational Technology, Zhejiang Gongshang University, Hangzhou Center for Disease Control and Prevention

Language: English

Topic: Antimicrobial Peptides and Activities

Subfield: Microbiology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,980