Inhibitory effects of phenylbutyrate on the proliferation, morphology, migration and invasiveness of malignant glioma cells

作者: Herbert H. Engelhard , Ronald J. Homer , Holly A. Duncan , Jack Rozental

DOI: 10.1023/A:1005865125588

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摘要: The purpose of this study was to characterize the effects sodium 4-phenylbutyrate (phenylbutyrate) on proliferation, morphology, migration and invasiveness malignant glioma cells in vitro. Phenylbutyrate is a novel differentiating cytotoxic compound used clinically with low toxicity treatment beta-thalassemia, sickle cell anemia urea cycle disorders. Preliminary clinical trials testing phenylbutyrate as an anti-cancer agent have included patients glioma. However, little information available regarding cells, particularly respect expression genes important pathogenesis glial malignancy. In experiments reported here, lines explant from tumor patient were exposed 2, 4 8 mM compared untreated control cells. effect cellular proliferation assessed using counts DNA flow cytometry. Changes morphology evaluated vimentin staining. Scratch Matrigel assays performed assess changes invasiveness. Finally, Northern blot analysis c-myc urokinase expression. found dose-dependent inhibitory migration, Mean growth-inhibitory (IC50) concentrations ranged 0.5 for T98G 5.0 reduced % S phase increased G0/G1 produced morphologic consistent induction differentiation. 24 hours resulted 50% reduction blots showed decrease at non-cytotoxic doses. We conclude that promising candidate treating

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