| 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
|
| Resource |
| Mice |
RBRC02388 |
