Department of Anesthesiology, Handan Central Hospital, Handan, Hebei, China.
Department of Anesthesiology, Handan Central Hospital, Handan, Hebei, China.
Brain Res. 2021 Sep 15;1767:147543. doi: 10.1016/j.brainres.2021.147543. Epub 2021 Jun 3.
Sevoflurane is a common inhalational anesthetic, which has been revealed to have anticancer effect in glioma. However, the mechanisms of sevoflurane in glioma progression remain largely unclear.
Cell proliferation, cell cycle, apoptosis and metastasis were monitored by cell counting kit-8 (CCK-8), flow cytometry, Transwell and Western blot assays. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot assays were used to examine the expression levels of circ_0079593, microRNA (miR)-633 and ROCK1 (Rho Associated Coiled-Coil Containing Protein Kinase 1). The dual-luciferase reporter assay was employed to confirm the targeting relationship between miR-633 and circ_0079593 or ROCK1. Animal experiment was conducted to explore the effect of sevoflurane in vivo.
Sevoflurane inhibited glioma cell proliferation, metastasis and induced apoptosis in vitro as well as impeded tumor growth in vivo. The expression of circ_0079593 was higher in glioma tissues and cells, and was decreased by sevoflurane treatment in glioma cells. Functional experiments showed that circ_0079593 overexpression in glioma cells reversed the inhibitory effects of sevoflurane on cell growth and metastasis. In a mechanism analysis, circ_0079593 acted as a sponge for miR-633 to elevate ROCK1 expression in glioma cells, and sevoflurane could regulate ROCK1 expression via circ_0079593/miR-633 axis. Besides that, circ_0079593/miR-633/ROCK1 axis mediated the protective effects of sevoflurane on glioma cell tumorigenesis.
Sevoflurane repressed glioma tumorigenesis via regulating circ_0079593/miR-633/ROCK1 axis, suggesting a new insight into the application of sevoflurane in glioma therapy.
七氟醚是一种常用的吸入性麻醉剂，已被证实具有抗脑胶质瘤作用。然而，七氟醚在胶质瘤进展中的作用机制在很大程度上尚不清楚。
通过细胞计数试剂盒-8（CCK-8）、流式细胞术、Transwell 和 Western blot 检测细胞增殖、细胞周期、凋亡和转移。实时定量聚合酶链反应（qRT-PCR）和 Western blot 检测检测 circ_0079593、微小 RNA（miR）-633 和 ROCK1（Rho 相关卷曲螺旋蛋白激酶 1）的表达水平。双荧光素酶报告实验用于证实 miR-633 与 circ_0079593 或 ROCK1 的靶向关系。动物实验用于探索七氟醚在体内的作用。
七氟醚抑制胶质瘤细胞的增殖、转移，并在体外诱导凋亡，同时抑制体内肿瘤生长。circ_0079593 在脑胶质瘤组织和细胞中的表达水平较高，七氟醚处理可降低胶质瘤细胞中的 circ_0079593 表达。功能实验表明，胶质瘤细胞中 circ_0079593 的过表达逆转了七氟醚对细胞生长和转移的抑制作用。在机制分析中，circ_0079593 作为 miR-633 的海绵，可提高胶质瘤细胞中 ROCK1 的表达，而七氟醚可通过 circ_0079593/miR-633 轴调节 ROCK1 的表达。此外，circ_0079593/miR-633/ROCK1 轴介导了七氟醚对胶质瘤细胞肿瘤发生的保护作用。
七氟醚通过调节 circ_0079593/miR-633/ROCK1 轴抑制脑胶质瘤的发生，为七氟醚在脑胶质瘤治疗中的应用提供了新的思路。
