Melittin Inhibits the Growth of Hepatocellular Carcinoma Huh7 Cells by Downregulating LARS2 and ZNF19

Abstract Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. Although surgery remains the most effective treatment, more than half of patients experience recurrent liver metastases within two years. This highlights the need for new therapeutic strategies driven by basic research. In this study, we used CCK-8 assays to evaluate the proliferation of liver cancer cells treated with melittin compared to controls. Proteomic sequencing was performed to identify differentially expressed proteins in Huh7 cells following melittin treatment. Two target genes, LARS2 and ZNF19, were further investigated using High Content Screening (HCS) to assess their roles in cell proliferation. CCK-8 results showed that melittin significantly reduced the viability of Huh7 and HepG2 cells at 24 and 48 hours in a dose-dependent manner. Proteomic analysis identified 142 upregulated and 8 downregulated proteins, while phosphoproteomic analysis revealed 88 upregulated and 21 downregulated phosphoproteins in the melittin-treated group. HCS assays demonstrated that silencing LARS2 and ZNF19 significantly inhibited liver cancer cell proliferation. These findings suggest that melittin suppresses the growth of Huh7 cells partly through downregulating LARS2and ZNF19.