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.Free PDF Download
To cite this article
H.-Y. Huang, Z.-J. Zhang, C.-B. Cao, N. Wang, F.-F. Liu, J.-Q. Peng, X.-J. Ren, J. Qian
The TLR4/NF-κB signaling pathway mediates the growth of colon cancer
Eur Rev Med Pharmacol Sci
Vol. 18 - N. 24