Kolodziej Malgorzata A, Gött Hanna, Kopischke Benjamin, Bender Michael K F, Weigand Markus A, Di Fazio Pietro, Schwarm Frank P, Uhle Florian
Department of Neurosurgery, Justus-Liebig University Giessen, D-35392 Giessen, Germany.
Department of Anaesthesiology, Heidelberg University Hospital, D-69120 Heidelberg, Germany.
Oncol Lett. 2021 Nov;22(5):759. doi: 10.3892/ol.2021.13020. Epub 2021 Sep 2.
Glioblastoma multiforme (GBM) is the most common malignant brain tumour in adults. The poor prognosis and short median overall survival of patients with GBM is associated with resistance to therapy after surgical and adjuvant treatment. The expression of various acetylcholine receptors (AChR) in GBM has been widely reported. The present study aimed to investigate the expression of cholinergic system-related genes in primary GBM and to explore the antiproliferative effect of 3-(2,4-dimethoxybenzylidene) anabaseine (GTS-21) in GBM cell lines. Therefore, the expression of 28 genes associated with the cholinergic system was detected using a customized RT Profiler PCR Array in 44 GBM and 5 healthy control brain tissue samples. In addition, the activity of GTS-21, an alpha 7 subunit nicotinic AChR (α7 nAChR) agonist, and that of α-bungarotoxin (α-BTX), an α7 nAChR antagonist, was determined in primary and established GBM cells. Therefore, the A172, U87 and G28 cell lines and primary GBM cells were treated with GTS-21, ACh or nicotine. Cell viability was evaluated using MTT assay at 24, 48 and 72 h following cell treatment with the corresponding compounds. The results revealed that the expression of cholinergic system-related components was notably downregulated, except that of cholinergic receptor nicotinic alpha 7 subunit (), in primary GBM and U87 cells. However, the dominant-negative duplicate form of was also downregulated. Furthermore, A172 and G28 cells exhibited a heterogeneous gene expression pattern. Additionally, GTS-21 inhibited the proliferation of GBM cells in a dose- and time-dependent manner. Interestingly, treatment with α-BTX restored the proliferation of U87 cells, but not that of A172 and G28 cells. Collectively, the findings of the present study suggested that GTS-21 may inhibit the proliferation of GBM cells and may therefore serve as a novel therapeutic approach to the treatment of GBM, which warrants further investigation.
多形性胶质母细胞瘤（GBM）是成人中最常见的恶性脑肿瘤。GBM患者预后差且中位总生存期短，这与手术和辅助治疗后的治疗耐药性有关。GBM中各种乙酰胆碱受体（AChR）的表达已被广泛报道。本研究旨在调查原发性GBM中胆碱能系统相关基因的表达，并探讨3-（2,4-二甲氧基苄叉）无叶豆碱（GTS-21）对GBM细胞系的抗增殖作用。因此，使用定制的RT Profiler PCR阵列检测了44例GBM和5例健康对照脑组织样本中与胆碱能系统相关的28个基因的表达。此外，还测定了原发性和已建立的GBM细胞中α7亚基烟碱型AChR（α7 nAChR）激动剂GTS-21和α7 nAChR拮抗剂α-银环蛇毒素（α-BTX）的活性。因此，用GTS-21、ACh或尼古丁处理A172、U87和G28细胞系以及原发性GBM细胞。在用相应化合物处理细胞后24、48和72小时，使用MTT法评估细胞活力。结果显示，除了胆碱能受体烟碱型α7亚基（）的表达外，原发性GBM和U87细胞中胆碱能系统相关成分的表达明显下调。然而，的显性负性重复形式也下调。此外，A172和G28细胞表现出异质的基因表达模式。此外，GTS-21以剂量和时间依赖性方式抑制GBM细胞的增殖。有趣的是，用α-BTX处理可恢复U87细胞的增殖，但不能恢复A172和G28细胞的增殖。总体而言，本研究结果表明，GTS-21可能抑制GBM细胞的增殖，因此可能成为治疗GBM的一种新的治疗方法，值得进一步研究。
