TY - JOUR
T1 - Effect of PPARδ Agonist on Stearoyl-CoA Desaturase 1 in Human Pancreatic Cancer Cells
T2 - Role of MEK/ERK1/2 Pathway
AU - Byagowi, Shima
AU - Naserpour Farivar, Taghi
AU - Najafipour, Reza
AU - Sahmani, Mehdi
AU - Darabi, Masoud
AU - Fayezi, Shabnam
AU - Mirshahvaladi, Shahab
AU - Darabi, Maryam
N1 - Funding Information:
This study was supported in part by a grant (No. 28/20/5423) from the Cellular and Molecular Research Center, Qazvin University of Medical Sciences. Support was also provided by the Liver and Gastrointestinal Disease Research Center at Tabriz University of Medical Sciences.
Publisher Copyright:
© 2015 Canadian Diabetes Association.
PY - 2015/4/1
Y1 - 2015/4/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84925081038&partnerID=8YFLogxK
U2 - 10.1016/j.jcjd.2014.09.006
DO - 10.1016/j.jcjd.2014.09.006
M3 - Journal articles
C2 - 25575964
AN - SCOPUS:84925081038
SN - 1499-2671
VL - 39
SP - 123
EP - 127
JO - Canadian Journal of Diabetes
JF - Canadian Journal of Diabetes
IS - 2
ER -
