Selective targeting of the TLR4 co-receptor, MD2, prevents colon cancer growth and lung metastasis.
Adult
Aged
Aged, 80 and over
Blotting, Western
Cell Line, Tumor
Cell Survival
/ drug effects
Chalcones
/ pharmacology
Colonic Neoplasms
/ complications
Enzyme-Linked Immunosorbent Assay
Gene Silencing
Humans
Immunoprecipitation
Lung Neoplasms
/ metabolism
Lymphocyte Antigen 96
/ antagonists & inhibitors
Male
Middle Aged
Neoplasm Metastasis
/ prevention & control
Real-Time Polymerase Chain Reaction
Signal Transduction
/ drug effects
Toll-Like Receptor 4
/ metabolism
MD2
NF-κB
TLR4
colitis-induced colon cancer
colon cancer
Journal
International journal of biological sciences
ISSN: 1449-2288
Titre abrégé: Int J Biol Sci
Pays: Australia
ID NLM: 101235568
Informations de publication
Date de publication:
2020
2020
Historique:
received:
06
08
2019
accepted:
03
02
2020
entrez:
27
3
2020
pubmed:
27
3
2020
medline:
25
9
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 32210720
doi: 10.7150/ijbs.39098
pii: ijbsv16p1288
pmc: PMC7085228
doi:
Substances chimiques
2,3-dimethoxy-4'-ethoxychalcone
0
Chalcones
0
LY96 protein, human
0
Lymphocyte Antigen 96
0
Toll-Like Receptor 4
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1288-1302Commentaires et corrections
Type : ErratumIn
Informations de copyright
© The author(s).
Déclaration de conflit d'intérêts
Competing Interests: The authors have declared that no competing interest exists.
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