Article
Induction of cell death in glioblastoma cells by Newcastle-Disease-Virus
Induktion von Zelltod bei Glioblastomzellen durch Newcastle-Disease-Virus
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Published: | April 23, 2004 |
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Outline
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Objective
Malignant gliomas remain incurable brain tumours despite aggressive treatment with surgery, irradiation and chemotherapy. As a new approach, therapy with different kinds of viruses, for instance genetically engineered, is generating more and more interest. Some naturally occurring strains of Newcastle-Disease-Virus (NDV) may have oncolytic potential against tumour cells. We have therefore investigated whether NDV may induce cell death in glioblastoma cells.
Methods
We analysed the effects of lytic and non-lytic strains of NDV on two established glioblastoma cell lines (U87, U138) with regard to parameters of cell death. For this purpose the tumour cells were treated with NDV at concentrations from 0.0001 up to 100 HU (haemagglutination units) for up to 96h. At different time points cell viability was measured using the tetrazolium salt WST-1. Additionally the induction of apoptotic parameters including cytokines was investigated by FACS analysis, ELISA and quantitative RT-PCR.
Results
All three NDV strains induced cell death in both glioblastoma cell lines in a dose-dependent manner. However, the most significant effects were observed with the lytic NDV strains. In parallel we observed modulation of distinct key parameters in the apoptotic signalling pathway, especially TNF-RII, Fas, Fas-L, TNF-alpha and IL-8 expression.
Conclusions
Oncolytic strains of NDV, apathogenic for human, seem to be a very promising option for therapy of glioblastoma. The in vitro results require in vivo testing using an animal model as the next step towards therapeutical application.