Department of Anesthesiology and Perioperative Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China.
Department of Anesthesiology and Perioperative Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China.
Life Sci. 2020 Sep 1;256:117897. doi: 10.1016/j.lfs.2020.117897. Epub 2020 Jun 2.
Glioma is the most common brain malignancy and surgical resection is the primary option for patient with glioma. Anesthetics could be used to inhibit cancer dissemination and metastasis during surgery. This study aims to assess the function of volatile anesthetic sevoflurane in glioma migration and invasion and explore the potential mechanism. Twenty-five patients with glioma were recruited in this study. LN229 and U251 cells were used in vitro experiments. Cell viability was analyzed by MTT analysis. Cell migration and invasion were examined via transwell analysis. microRNA-34a-5p (miR-34a-5p) and matrix metalloproteinase-2 (MMP-2) levels were measured via quantitative real-time polymerase chain reaction. The relationship of miR-34a-5p and MMP-2 was tested via bioinformatics analysis, luciferase reporter analysis, RNA immunoprecipitation and RNA pull-down. Sevoflurane decreased glioma cell migration and invasion. In glioma cells, sevoflurane up-regulated miR-34a-5p abundance and down-regulated MMP-2 level. Overexpression of miR-34a-5p contributed to sevoflurane-caused suppression of migration and invasion, while its knockdown played an opposite effect. MMP-2 was targeted via miR-34a-5p and MMP-2 silence reversed the influence of miR-34a-5p knockdown under sevoflurane. Sevoflurane exposure represses cell migration and invasion, which might be related to inhibition of MMP-2 by up-regulating miR-34a-5p. This study provides a novel mechanism for understanding the pharmacological effects of sevoflurane on glioma.
神经胶质瘤是最常见的脑恶性肿瘤，手术切除是神经胶质瘤患者的主要选择。麻醉剂可用于抑制手术过程中的癌症扩散和转移。本研究旨在评估挥发性麻醉剂七氟醚在神经胶质瘤迁移和侵袭中的作用，并探讨其潜在机制。本研究纳入 25 例神经胶质瘤患者。在体外实验中使用 LN229 和 U251 细胞。通过 MTT 分析检测细胞活力。通过 Transwell 分析检测细胞迁移和侵袭。通过定量实时聚合酶链反应检测 microRNA-34a-5p（miR-34a-5p）和基质金属蛋白酶-2（MMP-2）水平。通过生物信息学分析、荧光素酶报告分析、RNA 免疫沉淀和 RNA 下拉试验检测 miR-34a-5p 和 MMP-2 的关系。七氟醚降低神经胶质瘤细胞迁移和侵袭。在神经胶质瘤细胞中，七氟醚上调 miR-34a-5p 的丰度并下调 MMP-2 水平。miR-34a-5p 的过表达有助于七氟醚引起的迁移和侵袭抑制，而其敲低则起到相反的作用。MMP-2 是 miR-34a-5p 的靶标，MMP-2 沉默逆转了七氟醚下 miR-34a-5p 敲低的影响。七氟醚暴露抑制细胞迁移和侵袭，这可能与通过上调 miR-34a-5p 抑制 MMP-2 有关。本研究为理解七氟醚对神经胶质瘤的药理学作用提供了新的机制。
