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• W3148545388 abstract "Continuous exposure of breast cancer cells to adriamycin induces high expression of P-gp and multiple drug resistance. However, the biochemical process and the underlying mechanisms for the gradually induced resistance are not clear. To explore the underlying mechanism and evaluate the anti-tumor effect and resistance of adriamycin, the drug-sensitive MCF-7S and the drug-resistant MCF- 7Adr breast cancer cells were used and treated with adria- mycin, and the intracellular metabolites were profiled using gas chromatography mass spectrometry. Principal compo- nents analysis of the data revealed that the two cell lines showed distinctly different metabolic responses to adria- mycin. Adriamycin exposure significantly altered metabolic pattern of MCF-7S cells, which gradually became similar to the pattern of MCF-7Adr, indicating that metabolic shifts were involved in adriamycin resistance. Many intracellular metabolites involved in various metabolic pathways were significantly modulated by adriamycin treatment in the drug-sensitive MCF-7S cells, but were much less affected in the drug-resistant MCF-7Adr cells. Adriamycin treatment markedly depressed the biosynthesis of proteins, purines, pyrimidines and glutathione, and glycolysis, while it enhanced glycerol metabolism of MCF-7S cells. The ele- vated glycerol metabolism and down-regulated glutathione biosynthesis suggested an increased reactive oxygen spe- cies (ROS) generation and a weakened ability to balance ROS, respectively. Further studies revealed that adriamycin increased ROS and up-regulated P-gp in MCF-7S cells, which could be reversed by N-acetylcysteine treatment. It is suggested that adriamycin resistance is involved in slowed metabolism and aggravated oxidative stress. Assessment of cellular metabolomics and metabolic markers may be used to evaluate anti-tumor effects and to screen for candidate anti-tumor agents." @default.
• W3148545388 created "2021-04-13" @default.
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• W3148545388 date "2013-01-01" @default.
• W3148545388 modified "2023-09-27" @default.
• W3148545388 title "Metabolomic approach to evaluating adriamycin pharmacodynamics and resistance in breast cancer cells" @default.
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• W3148545388 hasPublicationYear "2013" @default.
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