PMID- 19258429
OWN - NLM
STAT- MEDLINE
DCOM- 20090608
LR  - 20220309
IS  - 1535-7163 (Print)
IS  - 1535-7163 (Linking)
VI  - 8
IP  - 3
DP  - 2009 Mar
TI  - Tolfenamic acid enhances pancreatic cancer cell and tumor response to radiation 
      therapy by inhibiting survivin protein expression.
PG  - 533-42
LID - 10.1158/1535-7163.MCT-08-0405 [doi]
AB  - 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.
FAU - Konduri, Santhi
AU  - Konduri S
AD  - Cancer Research Institute, M. D. Anderson Cancer Center Orlando, 110 Bonnie Loch 
      Court, Mail Point 47, Orlando, FL 32806, USA.
FAU - Colon, Jimmie
AU  - Colon J
FAU - Baker, Cheryl H
AU  - Baker CH
FAU - Safe, Stephen
AU  - Safe S
FAU - Abbruzzese, James L
AU  - Abbruzzese JL
FAU - Abudayyeh, Ala
AU  - Abudayyeh A
FAU - Basha, Md Riyaz
AU  - Basha MR
FAU - Abdelrahim, Maen
AU  - Abdelrahim M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090303
PL  - United States
TA  - Mol Cancer Ther
JT  - Molecular cancer therapeutics
JID - 101132535
RN  - 0 (BIRC5 protein, human)
RN  - 0 (Inhibitor of Apoptosis Proteins)
RN  - 0 (Microtubule-Associated Proteins)
RN  - 0 (Radiation-Sensitizing Agents)
RN  - 0 (Survivin)
RN  - 0 (ortho-Aminobenzoates)
RN  - 3G943U18KM (tolfenamic acid)
SB  - IM
MH  - Adenocarcinoma/genetics/pathology/*radiotherapy
MH  - Animals
MH  - Apoptosis/drug effects/radiation effects
MH  - Down-Regulation/drug effects/radiation effects
MH  - Gene Expression Regulation, Neoplastic/drug effects/radiation effects
MH  - Humans
MH  - Inhibitor of Apoptosis Proteins
MH  - Male
MH  - Mice
MH  - Mice, Nude
MH  - Microtubule-Associated Proteins/*genetics
MH  - Pancreatic Neoplasms/genetics/pathology/*radiotherapy
MH  - Promoter Regions, Genetic/drug effects
MH  - Radiation Tolerance/*drug effects
MH  - Radiation-Sensitizing Agents/pharmacology/therapeutic use
MH  - Survivin
MH  - Tumor Cells, Cultured
MH  - Xenograft Model Antitumor Assays
MH  - ortho-Aminobenzoates/*pharmacology/therapeutic use
EDAT- 2009/03/05 09:00
MHDA- 2009/06/09 09:00
CRDT- 2009/03/05 09:00
PHST- 2009/03/05 09:00 [entrez]
PHST- 2009/03/05 09:00 [pubmed]
PHST- 2009/06/09 09:00 [medline]
AID - 1535-7163.MCT-08-0405 [pii]
AID - 10.1158/1535-7163.MCT-08-0405 [doi]
PST - ppublish
SO  - Mol Cancer Ther. 2009 Mar;8(3):533-42. doi: 10.1158/1535-7163.MCT-08-0405. Epub 
      2009 Mar 3.