TLR4 signaling promotes immune escape of human colon cancer cells by inducing immunosuppressive cytokines and apoptosis resistance.

This study investigated the expression and biological role of TLR4 in human colon cancer cells' growth and survival, and its potential as a target for colon cancer therapy. Reverse transcription polymerase chain reaction (RT-PCR) and flow cytometry (FCM) were used to detect the expression level of TLR4. MTT analysis was performed to evaluate cell proliferation and enzyme-linked immunosorbent assay (ELISA) to test the production of IL-8, VEGF, and TGF-beta. MAPKs and NF-kappaB were analyzed by Western blotting. Apoptosis was analyzed by flow cytometry with Annexin V and propidium iodide staining. The results showed that the human colon cancer cells HT-29, SW480, and Lovo all expressed TLR4 at both mRNA and protein levels, and TLR4 ligand LPS could not affect the expression of TLR4 and the proliferation of colon cancer cells. LPS increased phosphorylation of ERK1/2 and p38 and activated NF-kappaB. LPS promoted cytokine production, such as IL-8, VEGF, and TGF-beta. In addition, LPS induced resistance of human colon cancer cells to TRAIL-induced apoptosis and NF-kappaB activation was necessary for apoptosis resistance. The study identified the expression level of TLR4 in human colon cancer cells and TLR4 was functionally active. TLR4 may play important roles in promoting immune escape of human colon cancer cells by inducing immunosuppressive factors and apoptosis resistance.