Host defense peptide LL-37 is involved in the regulation of cell proliferation and production of pro-inflammatory cytokines in hepatocellular carcinoma cells

Recent studies on the roles and mechanisms of LL-37 have demonstrated that LL-37 can either serve as a tumor promoter or a tumor suppressor in different cancers. The expression and function of LL-37 in hepatocellular carcinoma (HCC), however, remain unclear. In the present study, we confirmed the down-regulation of LL-37 in HCC tissues and the synthetic LL-37 peptide reduced the viability of HCC cells in a dose-dependent manner. Furthermore, we demonstrated that LL-37 peptide significantly delayed G1-S transition in Huh7 but not in HepG2 cells by suppressing CyclinD1-CDK4-p21 checkpoint signaling pathway. However, LL-37 caused no obvious apoptosis both in Huh7 and HepG2 cells, though the expression of apoptosis-related genes was strongly changed through qRT-PCR analysis, hinting at the possibility that LL-37 participates in regulating the apoptosis of HCC cells, but may not the only mechanism. Besides, we also identified that LL-37 treatment strongly inhibited the mRNA expression of TLR4 both in Huh7 and HepG2 cells, accompanied with the reduced expression of genes responsible for pro-inflammatory cytokines, including IL-8 and IL-6. In conclusion, our research suggested that LL-37 may be associated with the development of HCC.