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

Abstract

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.