Department of Anesthesiology and Pain medicine, Graduate School of Medicine, Nippon Medical School, Tokyo 113-8603, Japan.
Division of Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Chelsea & Westminster Hospital, London SW10 9NH, UK.
Int J Mol Sci. 2021 Apr 21;22(9):4355. doi: 10.3390/ijms22094355.
Inhalational anesthetics was previously reported to suppress glioma cell malignancy but underlying mechanisms remain unclear. The present study aims to investigate the effects of sevoflurane and desflurane on glioma cell malignancy changes via microRNA (miRNA) modulation. The cultured H4 cells were exposed to 3.6% sevoflurane or 10.3% desflurane for 2 h. The miR-138, -210 and -335 expression were determined with qRT-PCR. Cell proliferation and migration were assessed with wound healing assay, Ki67 staining and cell count kit 8 (CCK8) assay with/without miR-138/-210/-335 inhibitor transfections. The miRNA downstream proteins, hypoxia inducible factor-1α (HIF-1α) and matrix metalloproteinase 9 (MMP9), were also determined with immunofluorescent staining. Sevoflurane and desflurane exposure to glioma cells inhibited their proliferation and migration. Sevoflurane exposure increased miR-210 expression whereas desflurane exposure upregulated both miR-138 and miR-335 expressions. The administration of inhibitor of miR-138, -210 or -335 inhibited the suppressing effects of sevoflurane or desflurane on cell proliferation and migration, in line with the HIF-1α and MMP9 expression changes. These data indicated that inhalational anesthetics, sevoflurane and desflurane, inhibited glioma cell malignancy via miRNAs upregulation and their downstream effectors, HIF-1α and MMP9, downregulation. The implication of the current study warrants further study.
吸入麻醉剂先前被报道可抑制神经胶质瘤细胞的恶性程度,但潜在机制尚不清楚。本研究旨在通过 microRNA(miRNA)调节来探讨七氟醚和地氟醚对神经胶质瘤细胞恶性变化的影响。将培养的 H4 细胞暴露于 3.6%七氟醚或 10.3%地氟醚中 2 小时。采用 qRT-PCR 测定 miR-138、-210 和-335 的表达。采用划痕愈合试验、Ki67 染色和细胞计数试剂盒 8(CCK8)试验(转染 miR-138/-210/-335 抑制剂)评估细胞增殖和迁移。还通过免疫荧光染色测定 miRNA 下游蛋白缺氧诱导因子-1α(HIF-1α)和基质金属蛋白酶 9(MMP9)。暴露于神经胶质瘤细胞的七氟醚和地氟醚抑制其增殖和迁移。七氟醚暴露增加了 miR-210 的表达,而地氟醚暴露则上调了 miR-138 和 miR-335 的表达。miR-138、-210 或-335 抑制剂的给药抑制了七氟醚或地氟醚对细胞增殖和迁移的抑制作用,与 HIF-1α 和 MMP9 表达的变化一致。这些数据表明,吸入麻醉剂七氟醚和地氟醚通过上调 miRNA 及其下游效应物 HIF-1α 和 MMP9 的表达来抑制神经胶质瘤细胞的恶性程度。本研究的意义需要进一步研究。