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 fiM 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 MM 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 MM ALP. ALP caused a dose-dependent inhibition of invasion by GaMg tumor spheroids into brain aggregates. After 168 h of 1.0 MM 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.
|Number of pages||7|
|Publication status||Published - Mar 1991|