The study found that the natural peptide LL‑37 actually helps liver cancer cells become more aggressive and spread, and it also blocks the anti‑cancer effects of vitamin D. In simple terms, more LL‑37 makes liver cancer worse, while reducing LL‑37 could let vitamin D work better against the disease.

The effect of cathelicidin hCAP18/LL-37 in hepatocellular carcinoma (HCC) metastasis remains unclear. Here, we confirmed that LL-37 expression enhanced endothelial-mesenchymal transition (EMT), migration and invasion in HCC cells. And the HER2/EGFR-MAPK/ERK signal participated in the process above. More frequent lung metastases were observed in an LL-37-overexpressing hematogenous metastasis model. Interestingly, 1,25(OH)₂D₃ together with si-LL-37 significantly enhanced 1,25(OH)₂D₃-induced inhibition of migration and invasion in PLC/PRF-5 cells, and also enhanced reversion of the EMT process. Therefore, LL-37 is involved in HCC metastases, and may act as an important factor to attenuate the inhibitory activity of 1,25(OH)₂D₃ on HCC metastasis. Targeting hCAP18/LL-37 may offer a potential strategy to improve the anticancer activity of 1,25(OH)₂D₃ in HCC therapy.