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

作者: Tetsuro Kikuchi , Yasufumi Nagata , Toshiaki Abe

DOI: 10.1023/A:1005753523949

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摘要: We analyzed the antiproliferative effect of simvastatin (SV), an inhibitor 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, on human glioma cell lines. Inhibition growth with SV was observed in all lines tested. Different culture conditions altered this inhibition growth: lower concentration fetal bovine serum (FBS) medium, higher inhibitory cells. On morphological examination, we found that most cells exposed to became rounded and proportion floating increased a time-dependent manner. Then examined whether exogenously added mevalonic acid reversed SV. Exogenous suppressed dose-dependent also enhanced expression low-density lipoprotein (LDL) receptor peroxidized LDL (p-LDL) cytotoxic had additive effects pLDL-induced cytotoxicity. In mouse model, inoculated into nude mice inhibited by intratumoral injection both LDL. These results indicate or metabolite cholesterol synthesis pathway is necessary for and/or should be further as potential therapeutic agents gliomas.

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