The Involvement of NF-κB/Klotho Signaling in Colorectal Cancer Cell Survival and Invasion

Lipopolysaccharide significantly increased invasion, cell proliferation, and phospho-NF-κB p65 and phospho-IGF-1R protein, but decreased klotho protein expression, cell apoptosis, and the percentage of sub G0/G1 cells in SW480 and HT29 colorectal cancer cells. In contrast, NF-κB inhibitor exhibited a counteract effect of lipopolysaccharide. Transfection of Toll-like receptor 4 shRNA significantly decreased phospho-NF-κB p65 and phospho-IGF-1R protein levels, invasion, but significantly increased klotho protein expression, cell apoptosis, and the percentage of sub G0/G1 in SW480 and HT29 cells. In conclusion, inflammation inhibits klotho gene expression in colorectal cancer cells through activation of Toll-like receptor 4 /NF-κB signal pathway.