title: Effect of PPARδ agonist on stearoyl-CoA desaturase 1 in human pancreatic cancer cells: role of MEK/ERK1/2 pathway.
abstract: OBJECTIVE
  The stearoyl-CoA desaturase 1 (SCD1), also known as Δ9-desaturase, is a regulatory enzyme in the cellular lipid modification process that has been linked to pancreatic cancer and diabetes. The aim of the present study was to investigate the effect of peroxisome proliferative-activated receptor δ (PPARδ) agonist and ERK1/2- and EGF receptor (EGFR)-dependent pathways on the expression of SCD1 in human pancreatic carcinoma cell line PANC-1.
  
  
  METHODS
  PANC-1 cells cultured in RPMI-1640 were exposed to the commonly used MEK inhibitor PD98059, EGFR-selective inhibitor AG1478, and PPARδ agonist GW0742. Changes in mRNA, protein expression and activity index of SCD1 were then determined using real-time reverse transcription polymerase chain reaction, Western blot and gas liquid chromatography, respectively.
  
  
  RESULTS
  The activity index and expression of SCD1 (p<0.01) decreased following treatment with PPARδ agonist at both mRNA and protein levels, whereas significant increases were observed after treatment with MEK or EGFR inhibitor. It was also found that the activity index of SCD1 were lower (p<0.01) in the combined treatment compared to the incubation with either inhibitor alone.
  
  
  CONCLUSIONS
  PPARδ and MEK/ERK1/2- and EGFR-dependent pathways affect the expression and activity of SCD1 in pancreatic cancer cells. Furthermore, the aforementioned kinase signalling pathways were involved in an inhibitory effect on the expression and activity of SCD1 in these cells, possibly via PPARδ activation.
authors.affiliation: Cellular and Molecular Research Center, Faculty of Medicine, Qazvin University of Medical Sciences, Qazvin, Iran.
authors.forename: Shima
authors.initials: S
authors.lastname: Byagowi
authors.affiliation: Cellular and Molecular Research Center, Faculty of Medicine, Qazvin University of Medical Sciences, Qazvin, Iran.
authors.forename: Taghi
authors.initials: T
authors.lastname: Naserpour Farivar
authors.affiliation: Cellular and Molecular Research Center, Faculty of Medicine, Qazvin University of Medical Sciences, Qazvin, Iran.
authors.forename: Reza
authors.initials: R
authors.lastname: Najafipour
authors.affiliation: Cellular and Molecular Research Center, Faculty of Medicine, Qazvin University of Medical Sciences, Qazvin, Iran.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Sahmani
authors.affiliation: Liver and Gastrointestinal Disease Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Masoud
authors.initials: M
authors.lastname: Darabi
authors.affiliation: Students Research Committee, Faculty of Medicine, Department of Anatomy and Cell Biology, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Shabnam
authors.initials: S
authors.lastname: Fayezi
authors.affiliation: Department of Biotechnology, Cellular and Molecular and Burns Research Centers, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Shahab
authors.initials: S
authors.lastname: Mirshahvaladi
authors.affiliation: Cellular and Molecular Research Center, Faculty of Medicine, Qazvin University of Medical Sciences, Qazvin, Iran. Electronic address: darabim@tbzmed.ac.ir.
authors.forename: Maryam
authors.initials: M
authors.lastname: Darabi
mesh_terms: D045744:Cell Line, Tumor; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000502:physiology; D047494:PPAR delta / Q000819:agonists*; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D013230:Stearoyl-CoA Desaturase / Q000187:drug effects*; D013844:Thiazoles / Q000494:pharmacology; D010636:Phenols; D013438:Sulfhydryl Compounds
chemical_list: D005419:Flavonoids; D047494:PPAR delta; D013230:Stearoyl-CoA Desaturase; D013844:Thiazoles; C479979:(4-(((2-(3-fluoro-4-(trifluoromethyl)phenyl)-4-methyl-1,3-thiazol-5-yl)methyl)sulfanyl)-2-methylphenoxy)acetic acid; D010636:Phenols; D013438:Sulfhydryl Compounds; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
keywords: GW0742; PD98059; PPARδ; acides gras; fatty acids; néoplasmes pancréatiques; pancreatic neoplasms; Δ9-desaturase; Δ9-désaturase