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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2010-2-1
pubmed:abstractText
Nonsteroidal anti-inflammatory drugs (NSAIDs) can inhibit cell growth and metastasis, and induce cell apoptosis in cancerous cells. They have been shown to reduce incidence and mortality of gastric cancer by an unknown mechanism. NSAIDs often exert their effects by Cox-2 inhibition, and Cox-2 is overexpressed in gastric cancer cells. Nevertheless, when gastric cancer cells were treated with different NSAIDs, the non-Cox-2-inhibiting R-flurbiprofen was most effective at reducing proliferation of gastric cancer cells in vitro. R-Flurbiprofen prevented the metastatic characteristics of gastric cancer cells in vitro, and reduced tumor size and metastasis in vitro, when gastric cancer cells were injected into nude mice. R-Flurbiprofen also affected multidrug resistance, increasing the sensitivity of resistant gastric cancer cells to chemotherapeutic agents. Mechanistically, R-flurbiprofen was found to have pleiotropic effects, changing levels of cell cycle factors like Cyclin D1 and CKD4, apoptotic protwins like caspase3 and Bcl-2, and protwins that affect metastasis, like metalloproteases. Consistent with reports on other cancer cell types, NSAID treatment with R-flurbiprofen increased levels of the tumor suppressor neurotrophin receptor (p75(NTR)) in gastric cancer cells. The anticancer effects of R-flurbiprofen were found to require induction of p75(NTR) via the p38 signaling pathway, suggesting a possible mechanism of action.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1543-8392
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
7
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
156-68
pubmed:meshHeading
pubmed-meshheading:19916560-Animals, pubmed-meshheading:19916560-Anti-Inflammatory Agents, Non-Steroidal, pubmed-meshheading:19916560-Antineoplastic Agents, pubmed-meshheading:19916560-Apoptosis, pubmed-meshheading:19916560-Base Sequence, pubmed-meshheading:19916560-Cell Cycle, pubmed-meshheading:19916560-Cell Line, Tumor, pubmed-meshheading:19916560-Cell Movement, pubmed-meshheading:19916560-Cell Proliferation, pubmed-meshheading:19916560-Drug Resistance, Multiple, pubmed-meshheading:19916560-Flurbiprofen, pubmed-meshheading:19916560-Humans, pubmed-meshheading:19916560-Mice, pubmed-meshheading:19916560-Mice, Nude, pubmed-meshheading:19916560-Nerve Tissue Proteins, pubmed-meshheading:19916560-RNA, Small Interfering, pubmed-meshheading:19916560-Receptors, Nerve Growth Factor, pubmed-meshheading:19916560-Stomach Neoplasms, pubmed-meshheading:19916560-Xenograft Model Antitumor Assays
pubmed:year
2010
pubmed:articleTitle
R-flurbiprofen reverses multidrug resistance, proliferation and metastasis in gastric cancer cells by p75(NTR) induction.
pubmed:affiliation
State Key Laboratory of Cancer Biology & Xijing Hospital of Digestive Diseases, the Fourth Military Medical University, Department of Pharmacology, School of Pharmacy, the Fourth Military Medical University, Shaanxi Province 710032, P. R. China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't