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Effect
of alkyl-lysophospholipid on glioblastoma cell invasion into fetal rat brain
tissue in vitro
Engebraaten O, Bjerkvig
R, Berens ME
Gade Institute,
Department of Pathology, University of Bergen, Norway
The antitumor effect of alkyl-lysophospholipid (ALP) was studied on a continuous
glioma cell line (GaMg) as well as on tumor spheroids obtained from three
different primary brain tumor biopsies.
GaMg monolayer growth was reduced by 50%
after treatment with 30 microM ALP; cells accumulated in the G2M phase of the
cell cycle as determined by flow-cytometric analyses.
Tumor spheroid growth was
reduced by 25 and 44% during treatment with 10 and 30 microM ALP, respectively.
These drug concentrations also caused a severe destruction of spheroids.
No
effect on growth or morphology was seen in spheroids treated with 0.1 and 1.0
microM ALP.
ALP caused a dose-dependent inhibition of invasion by GaMg tumor
spheroids into brain aggregates.
After 168 h of 1.0 microM ALP treatment, the
volume of the intact brain aggregate was 90% larger than that in the untreated
co-cultures.
To further investigate the efficacy of ALP as an anti-invasive
drug, co-cultures were performed with specimens obtained from three primary
brain tumors: a highly invasive glioblastoma multiforme, an anaplastic
astrocytoma, and an astrocytoma.
Treatment of spheroids from the most invasive
tumor with ALP caused a 7-fold preservation of normal brain tissue relative to
control co-cultures.
Moreover, the sensitivity of primary glioma spheroids to
the anti-invasive effect of ALP seemed to be associated with the aggressiveness
of the tumor; spheroids from the more malignant specimen (glioblastoma
multiforme) were more sensitive than those from the less aggressive tumors.
The
anti-invasive effect seen with nontoxic concentrations of ALP may prove valuable
in the treatment of malignant gliomas.
PMID: 1998962 [PubMed - indexed for MEDLINE]
Source:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1998962&dopt=Abstract
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