Linked Life Data

11758830

Source:http://linkedlifedata.com/resource/pubmed/id/11758830

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
25-26
pubmed:dateCreated
2001-12-7
pubmed:abstractText
Limited clinical and experimental studies indicate that nonsteroidal anti-inflammatory drugs (NSAIDs) may inhibit gastric cancer growth. However, the mechanisms involved are not completely understood and cannot be explained by COX-2 inhibition alone. MAPK signaling pathway is essential for cell proliferation, but the effect of NSAIDs on MAPK activity and phosphorylation in gastric cancer has never been studied. Since increased and unregulated cell proliferation and reduced cell apoptosis are important features of cancer growth, we studied whether NS-398, a selective COX-2 inhibitor and/ or indomethacin (IND), a non-selective NSAID: 1) inhibit gastric cancer cell proliferation, 2) whether this inhibition is mediated via MAPK (ERK2), and 3) whether NSAIDs enhance apoptosis in gastric cancer cells. Human gastric epithelial cells (MKN28) derived from gastric tubular adenocarcinoma were cultured and treated with either vehicle, IND (0.25-0.5mM) or NS-398 (50-100 microM) for 6, 16, 24 and 48h. Studies: 1) Cellular proliferation was determined by 3H-thymidine uptake. 2) MAPK activity was measured by incorporation of radiolabeled phosphate into myelin basic protein. 3) Apoptosis was evaluated using TUNEL assay. IND and NS-398 significantly inhibited the proliferation of MKN28 cells at 24h by 3.5 - 5 fold (p<0.002) and at 48h by 2.5 - 10 fold (p<0.02). Both NSAIDs also significantly inhibited ERK2 activity: IND >53% inhibition, NS-398, 100 microM >72% inhibition; all p<0.05. Both IND and NS-398 significantly increased apoptotic index. In conclusion, IND and NS-398 significantly inhibit proliferation and growth of human gastric cancer cell line MKN28. This effect is mediated by NSAID-induced inhibition of MAPK (ERK2) kinase signaling pathway, essential for cell proliferation. NSAIDs also increase apoptosis in MKN28 cells. In addition to inhibiting cyclooxygenase, NSAIDs inhibit phosphorylating enzymes--kinases essential for signaling cell proliferation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0024-3205
pubmed:author
pubmed:issnType
Print
pubmed:day
9
pubmed:volume
69
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3045-54
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:11758830-Adenocarcinoma, pubmed-meshheading:11758830-Anti-Inflammatory Agents, Non-Steroidal, pubmed-meshheading:11758830-Apoptosis, pubmed-meshheading:11758830-Cell Division, pubmed-meshheading:11758830-Cyclooxygenase Inhibitors, pubmed-meshheading:11758830-DNA, pubmed-meshheading:11758830-Dose-Response Relationship, Drug, pubmed-meshheading:11758830-Drug Screening Assays, Antitumor, pubmed-meshheading:11758830-Humans, pubmed-meshheading:11758830-In Situ Nick-End Labeling, pubmed-meshheading:11758830-Indomethacin, pubmed-meshheading:11758830-Mitogen-Activated Protein Kinase 1, pubmed-meshheading:11758830-Nitrobenzenes, pubmed-meshheading:11758830-Stomach Neoplasms, pubmed-meshheading:11758830-Sulfonamides, pubmed-meshheading:11758830-Thymidine, pubmed-meshheading:11758830-Tumor Cells, Cultured, pubmed-meshheading:11758830-ras Proteins
pubmed:year
2001
pubmed:articleTitle
MAPK (ERK2) kinase--a key target for NSAIDs-induced inhibition of gastric cancer cell proliferation and growth.
pubmed:affiliation
VA Medical Center, Long Beach, CA 90822, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S.