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In vitro and in vivo antiproliferative effects of simvastatin, an HMG-CoA reductase inhibitor, on human glioma cells

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Abstract

We analyzed the antiproliferative effect of simvastatin (SV),an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase,on human glioma cell lines. Inhibition of cellgrowth with SV was observed in all celllines tested. Different culture conditions altered this inhibitionof growth: the lower the concentration of fetalbovine serum (FBS) in the medium, the higherthe inhibitory effect of SV on glioma cells.On morphological examination, we found that most ofthe cells exposed to SV became rounded andthe proportion of floating cells was increased ina time-dependent manner. Then we examined whether exogenouslyadded mevalonic acid reversed the growth inhibitory effectof SV. Exogenous mevalonic acid suppressed the inhibitoryeffect of SV on glioma cells in adose-dependent manner. SV also enhanced the expression oflow-density lipoprotein (LDL) receptor on glioma cells. Wealso found that peroxidized LDL (p-LDL) was cytotoxicto glioma cells and that SV had additiveeffects on pLDL-induced cytotoxicity. In a mouse model,growth of glioma cells inoculated into nude micewas inhibited by intratumoral injection of both SVand peroxidized LDL. These results indicate that mevalonicacid or a metabolite in the cholesterol synthesispathway is necessary for the growth of gliomacells and that simvastatin and/or peroxidized LDL shouldbe examined further as potential therapeutic agents forgliomas.

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Kikuchi, T., Nagata, Y. & Abe, T. In vitro and in vivo antiproliferative effects of simvastatin, an HMG-CoA reductase inhibitor, on human glioma cells. J Neurooncol 34, 233–239 (1997). https://doi.org/10.1023/A:1005753523949

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