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 Feb 12;22(4):1826. doi: 10.3390/ijms22041826.
Inhalational anaesthetics were previously reported to promote ovarian cancer malignancy, but underlying mechanisms remain unclear. The present study aims to investigate the role of sevoflurane- or desflurane-induced microRNA (miRNA) changes on ovarian cancer cell behaviour. The cultured SKOV3 cells were exposed to 3.6% sevoflurane or 10.3% desflurane for 2 h. Expression of miR-138, -210 and -335 was determined with qRT-PCR. Cell proliferation and migration were assessed with wound healing assay, Ki67 staining and Cell Counting Kit-8 (CCK8) assay with or without mimic miR-138/-210 transfections. The miRNA downstream effector, hypoxia inducible factor-1α (HIF-1α), was also analysed with immunofluorescent staining. Sevoflurane or desflurane exposure to cancer cells enhanced their proliferation and migration. miR-138 expression was suppressed by both sevoflurane and desflurane, while miR-210 expression was suppressed only by sevoflurane. miR-335 expression was not changed by either sevoflurane or desflurane exposure. The administration of mimic miR-138 or -210 reduced the promoting effects of sevoflurane and desflurane on cancer cell proliferation and migration, in line with the HIF-1α expression changes. These data indicated that inhalational agents sevoflurane and desflurane enhanced ovarian cancer cell malignancy via miRNA deactivation and HIF-1α. The translational value of this work needs further study.
先前有报道称吸入性麻醉剂可促进卵巢癌恶性进展，但其中的潜在机制尚不清楚。本研究旨在探讨七氟醚或地氟醚诱导的 microRNA（miRNA）变化对卵巢癌细胞行为的作用。将培养的 SKOV3 细胞暴露于 3.6%七氟醚或 10.3%地氟醚中 2 小时。采用 qRT-PCR 检测 miR-138、-210 和-335 的表达。采用划痕愈合实验、Ki67 染色和细胞计数试剂盒（CCK8）检测细胞增殖和迁移，同时进行转染 mimic miR-138/-210 实验。还采用免疫荧光染色分析 miRNA 下游效应物缺氧诱导因子-1α（HIF-1α）。七氟醚或地氟醚暴露于癌细胞后可增强其增殖和迁移能力。两种麻醉剂均可抑制 miR-138 的表达，而仅七氟醚可抑制 miR-210 的表达。七氟醚或地氟醚暴露均不改变 miR-335 的表达。给予 mimic miR-138 或 -210 可降低七氟醚和地氟醚对癌细胞增殖和迁移的促进作用，同时 HIF-1α 的表达也发生改变。这些数据表明，吸入性麻醉剂七氟醚和地氟醚通过 miRNA 失活和 HIF-1α 增强卵巢癌细胞的恶性程度。这项工作的转化价值需要进一步研究。
