多omics分析揭示了用帕克利塔克塞尔和/或托波特坎治疗的大脑癌细胞的显著代谢变化
Ahlam M Semreen1,2, Leen Oyoun Alsoud1,2, Mohammad H Semreen1,2
1Research Institute of Medical and Health Sciences, University of Sharjah, Sharjah, 27272, United Arab Emirates.
Heliyon
|November 11, 2024
概括
这项研究探讨了帕克利塔塞尔和托波特干如何影响质母细胞瘤 (GBM) 细胞. 组合疗法显著改变了代谢和蛋白质基因特征,揭示了针对性GBM治疗的潜在新生物标志物.
科学领域:
- 在瘤学瘤学.
- 生物化学 生物化学
- 蛋白质组学是指蛋白质组学.
背景情况:
- 质母细胞瘤 (GBM) 是一种具有不良预后的侵袭性脑瘤.
- 由于GBM复杂的细胞环境和耐药性,目前的疗法面临着挑战.
- 识别对化疗的分子反应对于改善GBM治疗至关重要.
研究的目的:
- 为了研究U87质母细胞瘤细胞的代谢和蛋白质组变化,用帕克利塔克塞尔和托波特坎治疗.
- 为了评估帕克利塔塞尔和托波特坎对细胞特征的联合作用.
- 确定这些化疗剂所影响的潜在生物标志物和分子通路.
主要方法:
- U87质母细胞瘤细胞被用DMSO,帕克利塔塞尔,托波特干或其组合治疗.
- 使用超高性能液态染色学四极飞行时间质谱法 (UHPLC-Q-TOF) 进行了代谢分析.
- 蛋白质组分析发现显著失调的蛋白质.
- 统计分析包括单向ANOVA和稀疏部分最小平方差异分析 (sPLS-DA).
主要成果:
- 与DMSO对照组相比,帕克利塔克塞尔和托波特坎治疗显著改变了14种代谢物.
- 组合疗法导致11种显著失调的代谢物.
- 在治疗组中,共有79种蛋白质显著失调.
- 在组合组中,特定蛋白质 (EIF3F,GNB2L1,HINT2,RPA3) 的调高.
- 关键路径如核糖体,亡,HIF-1信号传递和糖解被组合治疗显著改变.
结论:
- 多omics分析有效地揭示了GBM细胞中化疗反应的分子机制.
- 与帕克利塔塞尔和托波特坎的联合治疗诱导了明显的代谢和蛋白质基因变化.
- 鉴定的分子变化和生物标志物可以为质母细胞瘤的向治疗开发提供信息.
- 研究结果支持个性化医疗保健策略,以改善患者在GBM治疗中的结果.
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