Hohmann Tim, Feese Kerstin, Greither Thomas, Ghadban Chalid, Jäger Vivian, Dehghani Faramarz, Grabiec Urszula
Institute of Anatomy and Cell Biology, Medical Faculty of Martin Luther University Halle-Wittenberg, Grosse Steinstrasse 52, 06108 Halle (Saale), Germany.
Center for Reproductive Medicine and Andrology, Martin Luther University Halle-Wittenberg, 06108 Halle (Saale), Germany.
Cancers (Basel). 2019 Jan 31;11(2):161. doi: 10.3390/cancers11020161.
The current treatment of glioblastoma is not sufficient, since they are heterogeneous and often resistant to chemotherapy. Earlier studies demonstrated effects of specific cannabinoid receptor (CB) agonists on the invasiveness of glioblastoma cell lines, but the exact mechanism remained unclear. Three human glioblastoma cell lines were treated with synthetic CB ligands. The effect of cannabinoids on microRNAs (miRs), Akt, and on the expression of proliferation and apoptosis markers were analyzed. Furthermore, in a model of organotypic hippocampal slice cultures cannabinoid mediated changes in the invasiveness were assessed. MicroRNAs and the activation of Akt which are related to cell migration, apoptosis, and proliferation were evaluated and found not to be associated with changes in the invasiveness after treatment with CB ligands. Also proliferation and/or apoptosis were not altered after treatment. The effects of cannabinoids on invasiveness could be blocked by the application of receptor antagonists and are likely mediated via CB₁/CB₂. In conclusion, our results suggest that cannabinoids can influence glioblastoma cell invasion in a receptor and cell type specific manner that is independent of proliferation and apoptosis. Thus, cannabinoids can potentially be used in the future as an addition to current therapy.
目前胶质母细胞瘤的治疗并不充分，因为它们具有异质性且往往对化疗耐药。早期研究表明特定大麻素受体（CB）激动剂对胶质母细胞瘤细胞系的侵袭性有影响，但确切机制仍不清楚。用合成CB配体处理三种人类胶质母细胞瘤细胞系。分析了大麻素对微小RNA（miR）、Akt以及增殖和凋亡标志物表达的影响。此外，在器官型海马切片培养模型中评估了大麻素介导的侵袭性变化。评估了与细胞迁移、凋亡和增殖相关的微小RNA和Akt的激活情况，发现其与CB配体处理后的侵袭性变化无关。处理后增殖和/或凋亡也未改变。大麻素对侵袭性的影响可通过应用受体拮抗剂来阻断，且可能通过CB₁/CB₂介导。总之，我们的结果表明大麻素可以以一种独立于增殖和凋亡的受体和细胞类型特异性方式影响胶质母细胞瘤细胞的侵袭。因此，大麻素未来有可能作为当前治疗的补充药物使用。
