去甲肾上腺素可能通过抑制 MMP-11 抑制人胶质母细胞瘤细胞培养物的迁移和侵袭。
Norepinephrine inhibits migration and invasion of human glioblastoma cell cultures possibly via MMP-11 inhibition.
机构信息
Department of Anesthesiology, University of Virginia, Charlottesville, VA 22908, USA; Department of Anesthesiology, Zhongshan Hospital Fudan University, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Department of Anesthesiology, University of Virginia, Charlottesville, VA 22908, USA.
出版信息
Brain Res. 2021 Apr 1;1756:147280. doi: 10.1016/j.brainres.2021.147280. Epub 2021 Jan 27.
PURPOSE
Growing evidence has shown that the stress hormones affect tumor progression. Patients with surgery to remove tumor often have increased norepinephrine during the perioperative period. However, the effect of norepinephrine on the progression of glioblastoma has not yet studied. Therefore, the present study aimed at investigating the effects of norepinephrine on the migration and invasion of the human glioblastoma U87 and U251 cell lines and the mechanism for the effects.
METHODS
The U87 and U251 cells were treated with 0, 0.1, 1, 5, 10 or 50 μM norepinephrine. A scratch wound healing assay and a transwell invasion assay were used to investigate cell migration and invasion, respectively. The Human Tumor Metastasis RT Profiler PCR Array was used to detect the expression of 84 genes known to be involved in metastasis.
RESULTS
Following norepinephrine treatment, the ability of the U87 and U251 cells to migrate and invade was significantly decreased. Human Tumor Metastasis RT Profiler PCR Array assay showed that matrix metallopeptidase-11 (MMP-11) was decreased following norepinephrine treatment. The β-adrenergic receptor blocker (AR) propranolol blunted the suppressive effect of norepinephrine on the migration and invasion of U251 cells but did not have such an effect on the invasion of U87 cells. MMP-11 silencing inhibited the migration and invasion of U87 and U251 cells. The Cancer Genome Atlas data showed that patients with higher expression of MMP-11 in the glioblastoma tissues had poorer prognosis.
CONCLUSION
Our results indicate that norepinephrine inhibits the migration and invasion of human glioblastoma cells. This effect may be mediated by the decrease of MMP-11. β-AR may be a regulatory factor for this effect in U251 cells.
目的
越来越多的证据表明，应激激素会影响肿瘤的进展。接受肿瘤切除术的患者在围手术期往往会增加去甲肾上腺素。然而，去甲肾上腺素对胶质母细胞瘤进展的影响尚未研究。因此，本研究旨在探讨去甲肾上腺素对人胶质母细胞瘤 U87 和 U251 细胞系迁移和侵袭的影响及其作用机制。
方法
用 0、0.1、1、5、10 或 50μM 去甲肾上腺素处理 U87 和 U251 细胞。划痕愈合实验和 Transwell 侵袭实验分别用于检测细胞迁移和侵袭。人肿瘤转移 RT Profiler PCR 阵列用于检测已知参与转移的 84 个基因的表达。
结果
去甲肾上腺素处理后，U87 和 U251 细胞的迁移和侵袭能力明显下降。人肿瘤转移 RT Profiler PCR 阵列检测显示，去甲肾上腺素处理后基质金属蛋白酶-11（MMP-11）表达下调。β-肾上腺素能受体阻滞剂（AR）普萘洛尔减弱了去甲肾上腺素对 U251 细胞迁移和侵袭的抑制作用，但对 U87 细胞的侵袭没有这种作用。MMP-11 沉默抑制了 U87 和 U251 细胞的迁移和侵袭。癌症基因组图谱数据显示，胶质母细胞瘤组织中 MMP-11 表达较高的患者预后较差。
结论
我们的结果表明，去甲肾上腺素抑制人胶质母细胞瘤细胞的迁移和侵袭。这种作用可能是通过 MMP-11 的减少介导的。β-AR 可能是 U251 细胞中这种作用的调节因子。
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