瓦博格效应
糖酵解
厌氧糖酵解
顺铂
癌细胞
代谢途径
生物
背景(考古学)
葡萄糖摄取
氧化磷酸化
细胞培养
癌症研究
新陈代谢
代谢组学
癌症
生物化学
内分泌学
生物信息学
遗传学
化疗
古生物学
胰岛素
作者
José António Afonso,Catarina Barbosa-Matos,Ricardo Silvestre,Joana Pereira-Vieira,Samuel M. Gonçalves,Camille Mendes-Alves,Píer Parpot,Joana Pinto,Ângela Carapito,Paula Guedes de Pinho,Lúcio Lara Santos,Adhemar Longatto‐Filho,Fátima Baltazar
出处
期刊:Cancers
[MDPI AG]
日期:2024-04-05
卷期号:16 (7): 1418-1418
标识
DOI:10.3390/cancers16071418
摘要
Advanced urothelial bladder cancer (UBC) patients are tagged by a dismal prognosis and high mortality rates, mostly due to their poor response to standard-of-care platinum-based therapy. Mediators of chemoresistance are not fully elucidated. This work aimed to study the metabolic profile of advanced UBC, in the context of cisplatin resistance. Three isogenic pairs of parental cell lines (T24, HT1376 and KU1919) and the matching cisplatin-resistant (R) sublines were used. A set of functional assays was used to perform a metabolic screening on the cells. In comparison to the parental sublines, a tendency was observed towards an exacerbated glycolytic metabolism in the cisplatin-resistant T24 and HT1376 cells; this glycolytic phenotype was particularly evident for the HT1376/HT1376R pair, for which the cisplatin resistance ratio was higher. HT1376R cells showed decreased basal respiration and oxygen consumption associated with ATP production; in accordance, the extracellular acidification rate was also higher in the resistant subline. Glycolytic rate assay confirmed that these cells presented higher basal glycolysis, with an increase in proton efflux. While the results of real-time metabolomics seem to substantiate the manifestation of the Warburg phenotype in HT1376R cells, a shift towards distinct metabolic pathways involving lactate uptake, lipid biosynthesis and glutamate metabolism occurred with time. On the other hand, KU1919R cells seem to engage in a metabolic rewiring, recovering their preference for oxidative phosphorylation. In conclusion, cisplatin-resistant UBC cells seem to display deep metabolic alterations surpassing the Warburg effect, which likely depend on the molecular signature of each cell line.
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