Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of São Paulo, São Paulo 03001-000, Brazil.
Int J Mol Sci. 2020 Nov 9;21(21):8395. doi: 10.3390/ijms21218395.
The relationship between glioblastoma (GBM) and fatty acid metabolism could be the key to elucidate more effective therapeutic targets. 15-lipoxygenase-1 (15-LOX), a linolenic acid and arachidonic acid metabolizing enzyme, induces both pro- and antitumorigenic effects in different cancer types. Its role in glioma activity has not yet been clearly described. The objective of this study was to identify the influence of 15-LOX and its metabolites on glioblastoma cell activity.
GBM cell lines were examined using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) to identify 15-LOX metabolites. GBM cells treated with 15-LOX metabolites, 13-hydroxyoctadecadeinoic acid (HODE) and 9-HODE, and two 15-LOX inhibitors (luteolin and nordihydroguaiaretic acid) were also examined. Dose response/viability curves, RT-PCRs, flow cytometry, migration assays, and zymograms were performed to analyze GBM growth, migration, and invasion.
Higher quantities of 13-HODE were observed in five GBM cell lines compared to other lipids analyzed. Both 13-HODE and 9-HODE increased cell count in U87MG. 15-LOX inhibition decreased migration and increased cell cycle arrest in the G2/M phase.
15-LOX and its linoleic acid (LA)-derived metabolites exercise a protumorigenic influence on GBM cells in vitro. Elevated endogenous levels of 13-HODE called attention to the relationship between linoleic acid metabolism and GBM cell activity.
胶质母细胞瘤（GBM）与脂肪酸代谢之间的关系可能是阐明更有效治疗靶点的关键。15-脂氧合酶-1（15-LOX）是一种亚麻酸和花生四烯酸代谢酶，在不同类型的癌症中诱导促癌和抑癌作用。其在神经胶质瘤活性中的作用尚未得到明确描述。本研究的目的是确定 15-LOX 及其代谢物对胶质母细胞瘤细胞活性的影响。
使用高效液相色谱-串联质谱（HPLC-MS/MS）检测 GBM 细胞系，以鉴定 15-LOX 代谢物。还检测了用 15-LOX 代谢物 13-羟基十八碳烯酸（HODE）和 9-HODE 以及两种 15-LOX 抑制剂（木犀草素和 Nordihydroguaiaretic 酸）处理的 GBM 细胞。进行剂量反应/活力曲线、RT-PCR、流式细胞术、迁移测定和酶谱分析，以分析 GBM 生长、迁移和侵袭。
与分析的其他脂质相比，五种 GBM 细胞系中观察到更高量的 13-HODE。13-HODE 和 9-HODE 均增加 U87MG 中的细胞计数。15-LOX 抑制减少迁移并增加 G2/M 期的细胞周期停滞。
15-LOX 及其亚油酸（LA）衍生的代谢物在体外对 GBM 细胞发挥促肿瘤作用。内源性 13-HODE 水平升高引起了人们对亚油酸代谢与 GBM 细胞活性之间关系的关注。
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