Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q9UIJ5 (Rec)
 58,342 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Most experimental work addressing cyclooxygenase-2 (COX-2) inhibitor has focused on suppressing hematogenic spread. Little is known about the mechanism by which this inhibitor can also block lymphatic metastasis. Here, the effects of COX-2 inhibitor on vascular endothelial growth factor-C (VEGF-C) expression, lymphangiogenesis and lymph node metastasis were investigated. Utilizing the highly metastatic human lung adenocarcinoma cell line Anip973 and its parental line AGZY83-a, which has a low metastatic capacity, we found elevated VEGF-C and COX-2 immunoreactivity in Anip973 cells compared with AGZY83-a cells. Celecoxib down-regulated expression of VEGF-C mRNA and protein in Anip973 cells while PGE(2) up-regulated expression of VEGF-C mRNA and protein in AGZY83-a cells in a concentration-dependent manner. The expression of COX-2 and VEGF-C was significantly increased in xenografted Anip973 tumors compared with AGZY83-a tumors. The Anip973 tumors showed more lymphatic vessels and lymph node metastasis than the AGZY83-a tumors. In vivo, celecoxib decreased VEGF-C expression in Anip973 tumor-treated mice to a similar level to that in the AGZY83-a tumor-treated mice. Consistent with this decrease in VEGF-C expression, the density of lymphatic vessels and lymph node metastasis in Anip973 tumor-treated mice were suppressed to approximately that found in the AGZY83-a tumor-treated ones. Taken together, our results suggest that the differential expression of COX-2 and VEGF-C might help explain the different metastasis phenotype of lung adenocarcinoma cancer, and that COX-2 inhibitor mediates VEGF-C to block lymphangiogenesis and lymph node metastasis. Thus, COX-2 may be a potential therapeutic target for blocking lymph node metastasis in lung adenocarcinoma.
Anat Rec (Hoboken) 2009 Oct
PMID:Inhibition of cyclooxygenase-2 suppresses lymph node metastasis via VEGF-C. 1968 8

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.
Anat Rec (Hoboken) 2010 Nov
PMID:COX-2-mediated regulation of VEGF-C in association with lymphangiogenesis and lymph node metastasis in lung cancer. 2083 Jul 83