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Celecoxib synergizes human pancreatic ductal adenocarcinoma cells to sorafenib-induced growth inhibition.

Rosendahl, Ann LU ; Gundewar, Chinmay LU ; Said Hilmersson, Katarzyna LU ; Karnevi, Emelie LU and Andersson, Roland LU (2012) In Pancreatology 12(3). p.219-226
Abstract
BACKGROUND:

Pancreatic ductal adenocarcinoma is frequently associated with aberrant activation of the Ras/Raf/MAPK pathway and cyclooxygenase-2 (COX-2) overexpression. This study evaluated the potential for combining the multikinase inhibitor sorafenib and the specific COX-2 inhibitor celecoxib as therapy in pancreatic ductal adenocarcinoma cells.



METHODS:

BxPC-3, MIAPaCa-2, PANC-1 and AsPC-1 pancreatic adenocarcinoma cells were exposed to sorafenib and celecoxib combined treatment in vitro. Cell viability and various growth promoting and survival signaling pathways were monitored by MTT, flow cytometry and Western blotting.



RESULTS:

Combined treatment with sorafenib and... (More)
BACKGROUND:

Pancreatic ductal adenocarcinoma is frequently associated with aberrant activation of the Ras/Raf/MAPK pathway and cyclooxygenase-2 (COX-2) overexpression. This study evaluated the potential for combining the multikinase inhibitor sorafenib and the specific COX-2 inhibitor celecoxib as therapy in pancreatic ductal adenocarcinoma cells.



METHODS:

BxPC-3, MIAPaCa-2, PANC-1 and AsPC-1 pancreatic adenocarcinoma cells were exposed to sorafenib and celecoxib combined treatment in vitro. Cell viability and various growth promoting and survival signaling pathways were monitored by MTT, flow cytometry and Western blotting.



RESULTS:

Combined treatment with sorafenib and celecoxib synergistically inhibited pancreatic adenocarcinoma cell proliferation. This regimen produced combination index (CI) values between 0.67 and 0.92 for the various cell lines, indicating significant synergistic interactions between sorafenib and celecoxib, which also markedly inhibited the migratory capacity. The growth inhibition was associated with an accumulation of cells in the G(0)/G(1) phase of the cell cycle and induction of apoptosis. These changes were accompanied by a significant reduction of p21(WAF1/Cip1) levels, where celecoxib sensitized the cells to sorafenib-mediated p21(WAF1/Cip1) suppression.



CONCLUSION:

These results suggest that combined treatment with sorafenib and celecoxib synergistically induce growth inhibition and apoptosis in pancreatic adenocarcinoma cells through a process involving p21(WAF1/Cip1) suppression (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Pancreatology
volume
12
issue
3
pages
219 - 226
publisher
Karger
external identifiers
  • wos:000307127100009
  • pmid:22687377
  • scopus:84862156931
ISSN
1424-3903
DOI
10.1016/j.pan.2012.04.005
language
English
LU publication?
yes
id
7846d0db-5c45-4d90-a501-5cffe72bfee5 (old id 2859575)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/22687377?dopt=Abstract
date added to LUP
2012-07-04 12:36:39
date last changed
2017-01-01 07:32:46
@article{7846d0db-5c45-4d90-a501-5cffe72bfee5,
  abstract     = {BACKGROUND:<br/><br>
Pancreatic ductal adenocarcinoma is frequently associated with aberrant activation of the Ras/Raf/MAPK pathway and cyclooxygenase-2 (COX-2) overexpression. This study evaluated the potential for combining the multikinase inhibitor sorafenib and the specific COX-2 inhibitor celecoxib as therapy in pancreatic ductal adenocarcinoma cells.<br/><br>
<br/><br>
METHODS:<br/><br>
BxPC-3, MIAPaCa-2, PANC-1 and AsPC-1 pancreatic adenocarcinoma cells were exposed to sorafenib and celecoxib combined treatment in vitro. Cell viability and various growth promoting and survival signaling pathways were monitored by MTT, flow cytometry and Western blotting.<br/><br>
<br/><br>
RESULTS:<br/><br>
Combined treatment with sorafenib and celecoxib synergistically inhibited pancreatic adenocarcinoma cell proliferation. This regimen produced combination index (CI) values between 0.67 and 0.92 for the various cell lines, indicating significant synergistic interactions between sorafenib and celecoxib, which also markedly inhibited the migratory capacity. The growth inhibition was associated with an accumulation of cells in the G(0)/G(1) phase of the cell cycle and induction of apoptosis. These changes were accompanied by a significant reduction of p21(WAF1/Cip1) levels, where celecoxib sensitized the cells to sorafenib-mediated p21(WAF1/Cip1) suppression.<br/><br>
<br/><br>
CONCLUSION:<br/><br>
These results suggest that combined treatment with sorafenib and celecoxib synergistically induce growth inhibition and apoptosis in pancreatic adenocarcinoma cells through a process involving p21(WAF1/Cip1) suppression},
  author       = {Rosendahl, Ann and Gundewar, Chinmay and Said Hilmersson, Katarzyna and Karnevi, Emelie and Andersson, Roland},
  issn         = {1424-3903},
  language     = {eng},
  number       = {3},
  pages        = {219--226},
  publisher    = {Karger},
  series       = {Pancreatology},
  title        = {Celecoxib synergizes human pancreatic ductal adenocarcinoma cells to sorafenib-induced growth inhibition.},
  url          = {http://dx.doi.org/10.1016/j.pan.2012.04.005},
  volume       = {12},
  year         = {2012},
}