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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2009-3-16
pubmed:abstractText
Survivin is overexpressed in most human cancers, including pancreatic adenocarcinoma. Expression of survivin is regulated by specificity protein (Sp) proteins and related to resistance to radiation therapy. Tolfenamic acid induces Sp protein degradation in several cancer cell lines. The purpose of this study is to investigate whether tolfenamic acid inhibits survivin expression and sensitizes pancreatic cancer cells/tumor to radiotherapy. Panc1 and L3.6pl cells have been used to study the effect of radiation on survivin expression and to investigate the efficacy of tolfenamic acid in enhancing the response to radiation therapy. In addition, an orthotopic model for human pancreatic cancer has been used to confirm the efficacy of tolfenamic acid to enhance tumor response to radiation in vivo. Pancreatic cancer cell lines express variable levels of survivin mRNA/protein, which correlate with their radiosensitivity. Radiation increased survivin promoter activity and protein expression in Panc1 and L3.6pl cells and tolfenamic acid inhibited both constitutive and radiation-induced survivin protein expression and enhanced the response of pancreatic cancer cells to radiation therapy. In vivo studies show that tolfenamic acid enhanced the radiation-induced apoptosis associated with decreased survivin expression in tumors and this correlates with the enhanced response of these tumors to the radiation. Thus, tolfenamic acid significantly enhances pancreatic cancer cells/tumor response to radiation therapy. The underlying mechanism includes tolfenamic acid-induced degradation of Sp proteins, which in tumor decreases expression of the Sp-dependent antiapoptotic protein survivin. These preclinical data suggest that tolfenamic acid has the potential to increase the response of pancreatic adenocarcinoma to radiation therapy.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1535-7163
pubmed:author
pubmed:issnType
Print
pubmed:volume
8
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
533-42
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:19258429-Adenocarcinoma, pubmed-meshheading:19258429-Animals, pubmed-meshheading:19258429-Anthranilic Acids, pubmed-meshheading:19258429-Apoptosis, pubmed-meshheading:19258429-Down-Regulation, pubmed-meshheading:19258429-Gene Expression Regulation, Neoplastic, pubmed-meshheading:19258429-Humans, pubmed-meshheading:19258429-Inhibitor of Apoptosis Proteins, pubmed-meshheading:19258429-Male, pubmed-meshheading:19258429-Mice, pubmed-meshheading:19258429-Mice, Nude, pubmed-meshheading:19258429-Microtubule-Associated Proteins, pubmed-meshheading:19258429-Pancreatic Neoplasms, pubmed-meshheading:19258429-Promoter Regions, Genetic, pubmed-meshheading:19258429-Radiation Tolerance, pubmed-meshheading:19258429-Radiation-Sensitizing Agents, pubmed-meshheading:19258429-Tumor Cells, Cultured, pubmed-meshheading:19258429-Xenograft Model Antitumor Assays
pubmed:year
2009
pubmed:articleTitle
Tolfenamic acid enhances pancreatic cancer cell and tumor response to radiation therapy by inhibiting survivin protein expression.
pubmed:affiliation
Cancer Research Institute, M. D. Anderson Cancer Center Orlando, 110 Bonnie Loch Court, Mail Point 47, Orlando, FL 32806, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't