The TLR4/NF-κB signaling pathway mediates the growth of colon cancer.

OBJECTIVE We studied the involvement of the TLR4/NF-κB pathway in the growth of colon cancer using human colon cancer specimens, human colon cancer SW620 cell line, and nude mouse xenograft model. MATERIALS AND METHODS Tissue samples were surgically harvested. The human colon cancer SW620 cell line was pre-treated with the TLR4 inhibitor CRX-526 and stimulated with LPS. The nude mouse xenograft model was established by subcutaneous injection of SW620 cells with or without CRX-526, the TLR4 inhibitor. The study outcomes were mRNA and protein expressions of TLR4 and NF-κB p65 in specimens of colon cancer and adjacent normal tissue, SW620 cell line, and xenografts. In addition, we studied production of interleukin (IL)-6 and IL-8 in culture supernatants of LPS-stimulated SW620 cells. RESULTS Both mRNA and protein expressions of TLR4 and NF-κB in colon cancer specimens were higher than those in the adjacent normal tissue. LPS up-regulated expression of TLR4 and NF-κB, and stimulated production of IL-6 and IL-8 in SW620 cells. These effects were attenuated by CRX-526. TLR4 inhibition was also effective in the nude mouse xenograft model, as tumor sizes were significantly smaller, and expressions of TLR4 and NF-κB significantly lower, in the mice treated with CRX-526. CONCLUSIONS The TLR4/NF-κB signaling pathway is activated in colon cancer, causing production of IL-6 and IL-8, and, thereby, tumor growth and metastasization. Inhibition of TLR4 attenuates up-regulation of NF-κB and inhibits tumor growth.