The present study was designed to uncover the inhibitory effect of PON on epithelial-mesenchymal transition (EMT), migration and invasion of HCT116 cells induced by pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) in vitro, and liver metastasis in vivo.
Pathway analyses of all mutated genes in liver metastases showed aberrant tumor necrosis factor and transforming growth factor signaling in metastatic cells.
To investigate the role of TNF-α in the growth of pre-existing micrometastases in the liver following IR, we used a mouse model of colorectal liver metastases.
Vector experiments showed that the pd20-TNFα recombinant protein group had significantly reduced cancer lesions and liver metastasis in nude mice compared with the control group.
Our findings show that PCSK9 deficiency reduces liver metastasis by its ability to lower cholesterol levels and by possibly enhancing TNFα-mediated apoptosis.