Linked Life Data

20830783

Source:http://linkedlifedata.com/resource/pubmed/id/20830783

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2010-11-1
pubmed:abstractText
The mechanisms underlying the effects of COX-2 on tumor lymphangiogenesis remain largely undefined. Here, the human lung cancer cell lines A549, 95D, Anip973, and AGZY83-a with different metastatic capacities were investigated by immunostaining, western blotting, and real-time RT-PCR. We observed increased expressions of COX-2 and VEGF-C in the three highly metastatic cell lines compared with the less metastatic AGZY83-a cell line. The COX-2-specific inhibitor Celecoxib suppressed VEGF-C expression whereas the main COX-2 metabolite PGE(2) elevated VEGF-C expression in Anip973 and AGZY83-a cells in positive and negative experiments. To determine the functional link to COX-2 more specifically and elucidate the mechanistic pathway, we used a siRNA to knock down the high COX-2 expression in Anip973 cells and transfected a COX-2 cDNA to enhance the low COX-2 expression in AGZY83-a cells, and then treated the cells with EP1/EP4 agonists or antagonists, respectively. The results revealed that the EP1/EP4 agonists significantly increased VEGF-C production in the COX-2-knockdown Anip973 cells. In contrast, the EP1/EP4 antagonists diminished VEGF-C production in the COX-2-overexpressing AGZY83-a cells. Furthermore, animal models provided evidence that Celecoxib decreased VEGF-C expression, lymphangiogenesis, and lymph node metastases in Anip973 cells, whereas PGE(2) treatment increased the same factors in the parental AGZY83-a cells. A positive correlation between COX-2 and VEGF-C was also confirmed in vivo. The present data suggest that COX-2 regulates VEGF-C expression via the PGE(2) pathway, and that EP1/EP4 receptors are involved in PGE(2)-mediated VEGF-C production. Thus, COX-2 may represent a candidate gene for blocking tumor lymphangiogenesis and lymph node metastasis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1932-8494
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
293
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1838-46
pubmed:meshHeading
pubmed-meshheading:20830783-Adenocarcinoma, pubmed-meshheading:20830783-Animals, pubmed-meshheading:20830783-Cell Line, Tumor, pubmed-meshheading:20830783-Cyclooxygenase 2, pubmed-meshheading:20830783-Cyclooxygenase 2 Inhibitors, pubmed-meshheading:20830783-Dinoprostone, pubmed-meshheading:20830783-Disease Models, Animal, pubmed-meshheading:20830783-Humans, pubmed-meshheading:20830783-Lung Neoplasms, pubmed-meshheading:20830783-Lymphangiogenesis, pubmed-meshheading:20830783-Lymphatic Metastasis, pubmed-meshheading:20830783-Mice, pubmed-meshheading:20830783-Mice, Nude, pubmed-meshheading:20830783-Pyrazoles, pubmed-meshheading:20830783-RNA, Small Interfering, pubmed-meshheading:20830783-Sulfonamides, pubmed-meshheading:20830783-Transplantation, Heterologous, pubmed-meshheading:20830783-Vascular Endothelial Growth Factor C
pubmed:year
2010
pubmed:articleTitle
COX-2-mediated regulation of VEGF-C in association with lymphangiogenesis and lymph node metastasis in lung cancer.
pubmed:affiliation
Department of Anatomy, Harbin Medical University, Harbin, China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't