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胰腺癌细胞表现出较低的油酸氧化,其条件培养基抑制人肌管中的油酸氧化。

Pancreatic cancer cells show lower oleic acid oxidation and their conditioned medium inhibits oleic acid oxidation in human myotubes.

机构信息

Section for Pharmacology and Pharmaceutical Biosciences, Department of Pharmacy, University of Oslo, Norway.

Section for Pharmacology and Pharmaceutical Biosciences, Department of Pharmacy, University of Oslo, Norway.

出版信息

Pancreatology. 2020 Jun;20(4):676-682. doi: 10.1016/j.pan.2020.04.014. Epub 2020 Apr 22.

Abstract

BACKGROUND

/Objectives: We aimed to metabolically compare healthy primary human pancreatic epithelial cells (hPEC) to a pancreatic cancer cell line (PANC-1) and explore the effect on energy metabolism of exposing primary human myotubes to conditioned medium from hPEC and PANC-1 cells.

METHODS

Differences in metabolism were examined with radiolabeled glucose, oleic acid and lactic acid, and by qPCR. Mass spectrometry-based proteomics was used to study global protein secretion from the two cell types. Pathway analyses were performed.

RESULTS

PANC-1 cells tended to have higher glucose uptake, production of lactic acid, and glucose oxidation compared to hPEC cells. PANC-1 cells had higher uptake but lower oxidation of oleic acid, and mitochondrial reserve capacity from oleic acid was lower in PANC-1 cells. These differences in energy metabolism were reflected by differences in gene expressions and pathway analyses of the secretome. Conditioned medium from PANC-1 cells attenuated oleic acid oxidation in primary human myotubes.

CONCLUSIONS

Metabolic characterization of the PANC-1 cells revealed a glycolytic phenotype since they had an active glucose oxidation. Furthermore, PANC-1 cells showed a lower oleic acid oxidation and secreted a high amount of proteins into conditioned medium that also induced a reduced oleic acid oxidation in myotubes.

摘要

背景

/目的:我们旨在对健康的原代人胰腺上皮细胞(hPEC)与胰腺癌细胞系(PANC-1)进行代谢比较,并研究将 hPEC 和 PANC-1 细胞的条件培养基暴露于人原代肌管对能量代谢的影响。

方法

使用放射性标记的葡萄糖、油酸和乳酸以及 qPCR 检查代谢差异。基于质谱的蛋白质组学用于研究两种细胞类型的全局蛋白质分泌。进行了途径分析。

结果

与 hPEC 细胞相比,PANC-1 细胞的葡萄糖摄取、乳酸生成和葡萄糖氧化作用往往更高。PANC-1 细胞对油酸的摄取较高,但氧化较低,且来自油酸的线粒体储备能力在 PANC-1 细胞中较低。这些能量代谢差异反映在分泌组的基因表达和途径分析中。来自 PANC-1 细胞的条件培养基减弱了原代人肌管中油酸的氧化。

结论

PANC-1 细胞的代谢特征表明其具有活跃的葡萄糖氧化作用,表现出糖酵解表型。此外,PANC-1 细胞的油酸氧化较低,并分泌大量蛋白质进入条件培养基,这也导致肌管中的油酸氧化减少。

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