Article
Glioblastoma multiforme: in vitro and in vivo testing of new platin compounds
In-vitro- und In-vivo-Austestung neuer Platinverbindungen
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Published: | April 23, 2004 |
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Outline
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Objective
In spite of aggressive therapy, the prognosis of glioblastoma (GBM) is poor. New therapeutic strategies are needed to treat these highly malignant tumours. Terpyridin-Platin (II)-complexes were shown to bind to double-stranded DNA by intercalation and therefore can be considered as potential cytostatic drugs. 10 different Terpyridin-Platin II-complexes have been tested for the inhibition of the marker enzyme Thioredoxin-Reductase. One of them (I23N) was selected as the most effective agent.
Methods
Antiproliferative effect of I23N was tested on three GBM cell lines by BrdU ELISA using different concentrations and different application schemes. In the C6 glioma model the same compound was systemically applied to Wistar rats in two different doses (25 / 50mg/kg). MRIs were performed to follow-up the tumour growth course. Post mortem tumour tissues as well as normal tissues (kidney, liver, lung, skin, heart, muscle, gut) were collected to assess evidence for intoxication.
Results
In a single dose application scheme I23N inhibited tumour cell proliferation of all three GBM cultures dose dependently with IC50 values from 2.5-10.5 µM. This antiproliferative effect was even improved up to 2.2-6.9 µM when the compound was added 3x to the culture medium in 24h intervals. In vivo, a dose-dependent reduction of tumour growth of 123N-treated animals in comparison to untreated controls was observed as determined by MRI analysis. Histological evaluation of non-tumour tissues did not reveal any pathological alterations.
Conclusions
Our data indicate that I23N might be a good candidate for further preclinical evaluation to improve the observed anti-tumour effects.