过氧化物酶体增殖物激活受体 δ 激动剂对人胰腺癌细胞硬脂酰辅酶 A 去饱和酶 1 的影响：MEK/ERK1/2 通路的作用。
Effect of PPARδ agonist on stearoyl-CoA desaturase 1 in human pancreatic cancer cells: role of MEK/ERK1/2 pathway.
机构信息
Cellular and Molecular Research Center, Faculty of Medicine, Qazvin University of Medical Sciences, Qazvin, Iran.
Liver and Gastrointestinal Disease Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
出版信息
Can J Diabetes. 2015 Apr;39(2):123-7. doi: 10.1016/j.jcjd.2014.09.006. Epub 2015 Jan 6.
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.
目的
硬脂酰辅酶 A 去饱和酶 1（SCD1），也称为 Δ9-去饱和酶，是细胞脂质修饰过程中的一种调节酶，与胰腺癌和糖尿病有关。本研究旨在探讨过氧化物酶体增殖物激活受体 δ（PPARδ）激动剂以及 ERK1/2 和表皮生长因子受体（EGFR）依赖性通路对人胰腺癌细胞系 PANC-1 中 SCD1 表达的影响。
方法
在 RPMI-1640 中培养的 PANC-1 细胞暴露于常用的 MEK 抑制剂 PD98059、EGFR 选择性抑制剂 AG1478 和 PPARδ 激动剂 GW0742。然后使用实时逆转录聚合酶链反应、Western blot 和气相色谱分别测定 SCD1 的 mRNA、蛋白表达和活性指数的变化。
结果
PPARδ 激动剂处理后，SCD1 的活性指数和表达（p<0.01）在 mRNA 和蛋白水平上均降低，而 MEK 或 EGFR 抑制剂处理后则显著增加。还发现，与单独孵育抑制剂相比，联合处理时 SCD1 的活性指数更低（p<0.01）。
结论
PPARδ 和 MEK/ERK1/2 和 EGFR 依赖性通路影响胰腺癌细胞中 SCD1 的表达和活性。此外，上述激酶信号通路可能通过 PPARδ 激活参与抑制这些细胞中 SCD1 的表达和活性。
Zotero 插件