Linked Life Data

20878062

Source:http://linkedlifedata.com/resource/pubmed/id/20878062

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2010-9-29
pubmed:abstractText
Non-steroidal anti-inflammatory drugs (NSAIDs) attenuate tumor net growth in clinical and experimental cancer. Evaluations in cell culture experiments have implied involvement of growth factor and G-protein related signaling pathways to explain decreased proliferation, angiogenesis, increased cell adhesion and apoptosis. Sparse information is however available from studies on growing tumors in vivo. The aim of the present study was to map alterations in selected signal proteins in relation to heterogeneous tissue expression of COX-2 in tumors during COX inhibition. MCG 101 cells were exposed to indomethacin treatment both in vivo and in vitro to reduce PGE2 production. Tumor tissue specimens were taken for immunohistochemical analyses and qPCR determinations. Protein markers were selected to reflect cell proliferation and cell cycling, angiogenesis and metastasis in relationship to COX-2 staining in tumor tissue. Indomethacin did not change overall COX-2 staining in tumor tissue, but altered its distribution towards increased staining in cell nuclei/nucleoli and decreased COX-2 staining heterogeneity in tumor tissue. P53 staining was decreased, while PCNA and TGF?3 staining were increased by indomethacin in tumor areas with high presence of COX-2, which correlated to staining of BAX, TUNEL, Bcl-2, c-jun, p21, p27, p53 and NM23. Net tumor growth was predicted by EGF-R, p21 and p27 proteins in tumor tissue during indomethacin treatment (multivariate analysis). RNA transcript analyses showed decreased EGF-R and KRas expression in vivo, following indomethacin treatment, which also included KRas, PI3K, JAK1, STAT3 and c-jun, mRNAs in cultured tumor cells. In conclusion, our results extend earlier studies on cell culture experiments and demonstrate that EGF-R and downstream KRas pathways communicate effects of increased prostaglandin activity in tumor tissue in vivo.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1791-2423
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
37
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1143-52
pubmed:meshHeading
pubmed-meshheading:20878062-Animals, pubmed-meshheading:20878062-Anti-Inflammatory Agents, Non-Steroidal, pubmed-meshheading:20878062-Antineoplastic Agents, pubmed-meshheading:20878062-Apoptosis, pubmed-meshheading:20878062-Cell Line, Tumor, pubmed-meshheading:20878062-Cyclooxygenase 1, pubmed-meshheading:20878062-Cyclooxygenase 2, pubmed-meshheading:20878062-Cyclooxygenase Inhibitors, pubmed-meshheading:20878062-Female, pubmed-meshheading:20878062-Gene Expression, pubmed-meshheading:20878062-Immunohistochemistry, pubmed-meshheading:20878062-In Situ Nick-End Labeling, pubmed-meshheading:20878062-Indomethacin, pubmed-meshheading:20878062-Mice, pubmed-meshheading:20878062-Mice, Inbred C57BL, pubmed-meshheading:20878062-Neoplasms, Experimental, pubmed-meshheading:20878062-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:20878062-Signal Transduction
pubmed:year
2010
pubmed:articleTitle
Mechanisms behind COX-1 and COX-2 inhibition of tumor growth in vivo.
pubmed:affiliation
Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, Sahlgrenska University Hospital, SE 413 45 Gothenburg, Sweden.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't