Neurological Disease Center, The Third Affiliated Hospital of Chongqing Medical University, Yubei District, Chongqing, China.
Neurol Res. 2024 Dec;46(12):1105-1112. doi: 10.1080/01616412.2024.2395069. Epub 2024 Aug 28.
Glioblastoma (GBM) is a brain tumor with poor prognosis. Dexmedetomidine (Dex) regulates the biological behaviors of tumor cells to accelerate or decelerate cancer progression.
We investigated the effects of Dex on the migration, invasion, and glycolysis in GBM.
The concentration of Dex was determined using the cell counting kit-8 assay. The impacts of Dex on biological behaviors of GBM cells were assessed using Transwell assay, XF96 extracellular flux analysis, and western blot. The expression of c-Myc was examined using reverse transcription-quantitative polymerase chain reaction. The lactylation or stability of c-Myc was measured by western blot after immunoprecipitation or cycloheximide treatment.
We found that Dex (200 nM) inhibited GBM cell viability, migration, invasion, and glycolysis. C-Myc was highly expressed in GBM cells and was decreased by Dex treatment. Moreover, Dex suppressed lactylated c-Myc levels via suppressing glycolysis, thereby reducing the protein stability of c-Myc. Sodium lactate treatment abrogated the effects of Dex on the biological behaviors of GBM cells.
Dex suppressed the migration, invasion, and glycolysis of GBM cells via inhibiting lactylation of c-Myc and suppressing the c-Myc stability, suggesting that Dex may be a novel therapeutic drug for GBM treatment.
胶质母细胞瘤（GBM）是一种预后不良的脑肿瘤。右美托咪定（Dex）调节肿瘤细胞的生物学行为，从而加速或减缓癌症进展。
我们研究了 Dex 对 GBM 细胞迁移、侵袭和糖酵解的影响。
使用细胞计数试剂盒-8 测定 Dex 的浓度。通过 Transwell 测定、XF96 细胞外通量分析和 Western blot 评估 Dex 对 GBM 细胞生物学行为的影响。使用逆转录-定量聚合酶链反应检查 c-Myc 的表达。通过免疫沉淀或环己酰亚胺处理后 Western blot 测量 c-Myc 的乳酰化或稳定性。
我们发现 Dex（200 nM）抑制 GBM 细胞活力、迁移、侵袭和糖酵解。c-Myc 在 GBM 细胞中高表达，并被 Dex 处理下调。此外，Dex 通过抑制糖酵解抑制乳酰化 c-Myc 水平，从而降低 c-Myc 的蛋白稳定性。乳酸钠处理消除了 Dex 对 GBM 细胞生物学行为的影响。
Dex 通过抑制 c-Myc 的乳酰化和抑制 c-Myc 的稳定性来抑制 GBM 细胞的迁移、侵袭和糖酵解，表明 Dex 可能是治疗 GBM 的一种新的治疗药物。
