TLR4 Signaling Promotes Immune Escape of Human Colon Cancer Cells by Inducing Immunosuppressive Cytokines and Apoptosis Resistance

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Abstract:

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-β. MAPKs and NF-κB 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-κB. LPS promoted cytokine production, such as IL-8, VEGF, and TGF-β. In addition, LPS induced resistance of human colon cancer cells to TRAIL-induced apoptosis and NF-κB 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.

Keywords: Apoptosis resistance; Colon cancer; Immune escape; TLR4

Document Type: Research Article

DOI: http://dx.doi.org/10.3727/096504012X13425470196092

Publication date: January 1, 2012

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  • Formerly: Oncology Research Incorporating Anti-Cancer Drug Design
    Oncology Research Featuring Preclinical and Clincal Cancer Therapeutics publishes research of the highest quality that contributes to an understanding of cancer in areas of molecular biology, cell biology, biochemistry, biophysics, genetics, biology, endocrinology, and immunology, as well as studies on the mechanism of action of carcinogens and therapeutic agents, reports dealing with cancer prevention and epidemiology, and clinical trials delineating effective new therapeutic regimens.
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