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) 2 D 3 together with si-LL-37 significantly enhanced 1,25(OH) 2 D 3 -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) 2 D 3 on HCC metastasis. Targeting hCAP18/LL-37 may offer a potential strategy to improve the anticancer activity of 1,25(OH) 2 D 3 in HCC therapy.
Keyphrases
- induced apoptosis
- epithelial mesenchymal transition
- signaling pathway
- mouse model
- cell cycle arrest
- small cell lung cancer
- stem cells
- pi k akt
- poor prognosis
- cell death
- cell proliferation
- endoplasmic reticulum stress
- endothelial cells
- epidermal growth factor receptor
- mesenchymal stem cells
- high glucose
- diabetic rats
- climate change
- cancer therapy
- ionic liquid