Sevoflurane has been reported to have anti-tumorigenic effects in glioma. Circ_0000215 was found to play vital functions in the pathological progressions of glioma. However, whether circ_0000215 mediates the inhibitory effects of sevoflurane on glioma cells remains unclear. In vitro assays were performed using cell counting kit-8, flow cytometry, transwell and Western blot assays. The expression levels of circ_0000215, microRNA (miR)-1200 and NCR3LG1 (Natural Killer Cell Cytotoxicity Receptor 3 Ligand 1) were detected using quantitative real-time polymerase chain reaction (qRT-PCR) and/or Western blot. The dual-luciferase reporter assay and pull-down assay were used to investigate the relationship between miR-1200 and circ_0000215 or NCR3LG1. In vivo assay was conducted using xenograft nude mice model. In vitro assays suggested that sevoflurane repressed glioma cell proliferation, metastasis and induced apoptosis as well as hindered tumor growth in vivo, which were reversed by circ_0000215 overexpression. Mechanically, circ_0000215 was confirmed to directly target miR-1200, and NCR3LG1 was a target of miR-1200 in glioma cells. Importantly, circ_0000215 could regulate NCR3LG1 expression via miR-1200. Besides that, rescue assay suggested that circ_0000215 attenuated the inhibitory effects of sevoflurane on glioma cell growth and metastasis, which were reversed by miR-1200 overexpression or NCR3LG1 knockdown. Our study revealed that sevoflurane could suppress glioma tumorigenesis by regulating circ_0000215/miR-1200/NCR3LG1 axis, suggesting a new insight into the therapeutic potential of sevoflurane in glioma treatment.

据报道，七氟醚在胶质瘤中具有抗肿瘤发生作用。发现 Circ_0000215 在胶质瘤的病理进展中发挥重要作用。然而，circ_0000215是否介导七氟醚对胶质瘤细胞的抑制作用仍不清楚。使用细胞计数试剂盒-8、流式细胞术、transwell 和蛋白质印迹测定进行体外测定。使用定量实时聚合酶链反应 (qRT-PCR) 和/或蛋白质印迹检测 circ_0000215、microRNA (miR)-1200 和 NCR3LG1（天然杀伤细胞细胞毒性受体 3 配体 1）的表达水平。双荧光素酶报告基因分析和下拉分析用于研究 miR-1200 与 circ_0000215 或 NCR3LG1 之间的关系。体内使用异种移植裸鼠模型进行测定。体外试验表明，七氟醚抑制胶质瘤细胞增殖、转移和诱导细胞凋亡，并在体内阻碍肿瘤生长, 被 circ_0000215 过表达逆转。机械上，circ_0000215 被证实直接靶向 miR-1200，NCR3LG1 是 miR-1200 在胶质瘤细胞中的靶点。重要的是，circ_0000215 可以通过 miR-1200 调节 NCR3LG1 的表达。除此之外，救援试验表明，circ_0000215 减弱了七氟醚对胶质瘤细胞生长和转移的抑制作用，而这种抑制作用被 miR-1200 过表达或 NCR3LG1 敲低所逆转。我们的研究表明，七氟醚可以通过调节 circ_0000215/miR-1200/NCR3LG1 轴来抑制胶质瘤的发生，这为七氟醚在胶质瘤治疗中的治疗潜力提供了新的见解。