Article (Scientific journals)
The Anti-Tumor Effect of HDAC Inhibition in a Human Pancreas Cancer Model Is Significantly Improved by the Simultaneous Inhibition of Cyclooxygenase 2
Peulen, Olivier; Gonzalez, Arnaud; Peixoto, Paul et al.
2013In PLoS ONE, 8 (9), p. 75102
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Keywords :
PDAC; COX-2; HDAC; Celecoxib; CAM assay
Abstract :
[en] Pancreatic ductal adenocarcinoma is the fourth leading cause of cancer death worldwide, with no satisfactory treatment to date. In this study, we tested whether the combined inhibition of cyclooxygenase-2 (COX-2) and class I histone deacetylase (HDAC) may results in a better control of pancreatic ductal adenocarcinoma. The impact of the concomitant HDAC and COX-2 inhibition on cell growth, apoptosis and cell cycle was assessed first in vitro on human pancreas BxPC-3, PANC-1 or CFPAC-1 cells treated with chemical inhibitors (SAHA, MS-275 and celecoxib) or HDAC1/2/3/7 siRNA. To test the potential antitumoral activity of this combination in vivo, we have developed and characterized, a refined chick chorioallantoic membrane tumor model that histologically and proteomically mimics human pancreatic ductal adenocarcinoma. The combination of HDAC1/3 and COX-2 inhibition significantly impaired proliferation of BxPC-3 cells in vitro and stalled entirely the BxPC-3 cells tumor growth onto the chorioallantoic membrane in vivo. The combination was more effective than either drug used alone. Consistently, we showed that both HDAC1 and HDAC3 inhibition induced the expression of COX-2 via the NF-kB pathway. Our data demonstrate, for the first time in a Pancreatic Ductal Adenocarcinoma (PDAC) model, a significant action of HDAC and COX-2 inhibitors on cancer cell growth, which sets the basis for the development of potentially effective new combinatory therapies for pancreatic ductal adenocarcinoma patients.
Research center :
Giga-Cancer - ULiège
Disciplines :
Oncology
Author, co-author :
Peulen, Olivier   ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Département des sciences biomédicales et précliniques
Gonzalez, Arnaud  
Peixoto, Paul ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > GIGA-R : Labo de recherche sur les métastases
Turtoi, Andrei ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > GIGA-R : Labo de recherche sur les métastases
Mottet, Denis ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > GIGA-R : Labo de recherche sur les métastases
Delvenne, Philippe ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques
Castronovo, Vincenzo ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie générale et cellulaire
 These authors have contributed equally to this work.
Language :
English
Title :
The Anti-Tumor Effect of HDAC Inhibition in a Human Pancreas Cancer Model Is Significantly Improved by the Simultaneous Inhibition of Cyclooxygenase 2
Publication date :
11 September 2013
Journal title :
PLoS ONE
eISSN :
1932-6203
Publisher :
Public Library of Science, San Franscisco, United States - California
Volume :
8
Issue :
9
Pages :
e75102
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE]
CAC - Centre anticancéreux près l'Université de Liège asbl [BE]
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