Abstract

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.

Highlights

  • IntroductionThe standard therapy includes surgical dissection and an adjuvant radio- and chemotherapy

  • Glioblastoma is one of the most devastating tumors with a median survival time of 18 months [1].The standard therapy includes surgical dissection and an adjuvant radio- and chemotherapy.the current treatment is not sufficient, since glioblastomas are very heterogeneous and often radio- and chemoresistant [1]

  • MicroRNA Expression Is Not Affected by Cannabinoids

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Summary

Introduction

The standard therapy includes surgical dissection and an adjuvant radio- and chemotherapy. The current treatment is not sufficient, since glioblastomas are very heterogeneous and often radio- and chemoresistant [1]. This heterogeneity is reflected by different cells-of-origin and molecular subtypes [2]. The cells in individual glioma differ in their behavior regarding invasiveness, motility, morphology, genetics, susceptibility to therapy, and their ability to form tumors [3]. The resulting heterogeneous population of glioblastomas gives rise to the need for an improved understanding of tumor spreading and better or individualized therapeutic options. One potential novel therapeutic target might be the endocannabinoid system

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