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首页> 外文期刊>Journal of applied toxicology >Inhibitory effect of pisosterol on human glioblastoma cell lines with C-MYC amplification
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Inhibitory effect of pisosterol on human glioblastoma cell lines with C-MYC amplification

机译:猪油醇对人成胶质细胞瘤细胞系C-MYC扩增的抑制作用

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Despite the remarkable progress in the characterization of the molecular pathogenesis of glioblastoma multiforme (GBM>; these tumors remain incurable and, in most cases, refractory to aggressive cytotoxic treatments. We conducted a morphological and cytogenetic study in two GBM cell lines (U343 and AHOL1), before and after treatment with pisosterol (at 0.5,1.0 and 1.8 (xg ml1), a triterpene isolated from the fungus Pisolithus tinctorius. No significant alteration was observed in the morphology and frequency of chromosomal abnormalities in the cell lines analyzed after treatment with pisosterol. Using fluorescence in situ hybridization analysis with a locus-specific probe for C-MYC showed that 72% of U343 and 65% of AHOL1 cells contained more than two alleles of C-MYC before treatment. After treatment, no effects were detected at lower concentrations of pisosterol (0.5 and 1.0 |xg ml1). However, at 1.8 |xg ml1 of pisosterol, only 33% of U343 cells and 15% of AHOL1 cells presented more than two fluorescent signals, suggesting that pisosterol blocks the cells with gene amplification. Cells that do not show a high degree of C-MYC gene amplification have a less aggressive and invasive behavior and are easy targets for chemotherapy. Therefore, further studies are needed to examine the use of pisosterol in combination with conventional anti-cancer therapy.5 Supporting information may be found in the online version of this article.
机译:尽管在表征多形性胶质母细胞瘤(GBM>)的分子发病机理方面取得了显着进展,但这些肿瘤仍然无法治愈,并且在大多数情况下对积极的细胞毒性治疗无效。我们在两种GBM细胞系(U343和AHOL1)中进行了形态学和细胞遗传学研究),在用油甾醇(分别为0.5、1.0和1.8(xg ml1)处理)之前和之后,从真菌Pisolithus tinctorius分离出三萜烯,在用P.使用针对C-MYC的基因座特异性探针进行的荧光原位杂交分析表明,治疗前72%的U343和65%的AHOL1细胞包含两个以上的C-MYC等位基因,治疗后未发现任何作用。较低的猪甾醇浓度(0.5和1.0 | xg ml1),但是在1.8 | xg ml1的甾醇中,只有33%的U343细胞和15%的AHOL1细胞呈现出更多的t发出两个荧光信号,暗示了甾醇会通过基因扩增来阻断细胞。未显示高度C-MYC基因扩增的细胞具有较弱的侵袭性和侵袭性,并且很容易成为化学疗法的靶标。因此,需要进一步研究以研究将油甾醇与常规抗癌疗法联合使用。5可以在本文的在线版本中找到支持信息。

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