RRC ID 58936
Author Rajamanickam V, Yan T, Xu S, Hui J, Xu X, Ren L, Liu Z, Liang G, Wang O, Wang Y.
Title Selective targeting of the TLR4 co-receptor, MD2, prevents colon cancer growth and lung metastasis.
Journal Int J Biol Sci
Abstract Toll-like receptor (TLR) signaling is an emerging pathway in tumor cell invasion and metastasis. Myeloid differentiation protein-2 (MD2) contributes to ligand recognition and activation of TLRs in response to exogenous microbial insults or endogenous agents. We hypothesized that blocking MD2 using a specific inhibitor would prevent TLR4-mediated inflammatory responses and metastatic cancer growth. Here, we report that a MD2 inhibitor, L6H21, inhibited migration and invasion of LPS-activated colon cancer CT26.WT cells. These activities were accompanied by inhibition of nuclear factor-κB (NF-κB) activation, and thereby inhibition of the production of pro-inflammatory cytokines and adhesive molecules in colon cancer cells. Furthermore, L6H21 inhibited CT26.WT metastasis to the lung in BALB/c mice as well as suppressed colitis-induced colon cancer induced by azoxymethane/dextran sulfate sodium (AOM/DSS). Taken together, our results demonstrated that L6H21 suppressed tumor invasion and metastasis through blocking TLR4-MD2/NF-κB signaling axis. These findings reveal that inhibition of MD2 may be an important target for the development of colon cancer therapies.
Volume 16(8)
Pages 1288-1302
Published 2020-2-17
DOI 10.7150/ijbs.39098
PII ijbsv16p1288
PMID 32210720
PMC PMC7085228
MeSH Adult Aged Aged, 80 and over Blotting, Western Cell Line, Tumor Cell Survival / drug effects Chalcones / pharmacology Colonic Neoplasms / complications* Colonic Neoplasms / drug therapy Colonic Neoplasms / metabolism* Enzyme-Linked Immunosorbent Assay Gene Silencing Humans Immunoprecipitation Lung Neoplasms / metabolism* Lung Neoplasms / prevention & control Lung Neoplasms / secondary* Lymphocyte Antigen 96 / antagonists & inhibitors* Lymphocyte Antigen 96 / metabolism* Male Middle Aged Neoplasm Metastasis / prevention & control Real-Time Polymerase Chain Reaction Signal Transduction / drug effects Toll-Like Receptor 4 / metabolism*
IF 4.858
Times Cited 0
Mice RBRC02388