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Glycomic alterations are associated with multidrug resistance in human leukemia.

The international journal of biochemistry & cell biology (2012-05-15)
Zhaohai Zhang, Yongfu Zhao, Lili Jiang, Xiaoyan Miao, Huimin Zhou, Li Jia
ZUSAMMENFASSUNG

Correlations of disease phenotypes with glycosylation changes have been analyzed intensively in tumor biology field. In this study we describe glycomic alterations of multidrug resistance in human leukemia cell lines. Using multiple glycan profiling tools: real-time PCR for quantification of glycogenes, FITC-lectin binding for glycan profiling, and mass spectrometry for glycan composition, we compared the glycomics of drug-resistant K562/ADR cells with parental K562 line. The results showed that the expression of glycogenes, glycan profiling and N-glycan composition were different in K562/ADR cells, as compared with those in K562 cells, whereas O-glycans of the two cell lines showed no different mass spectra. Further analysis of the N-glycan regulation by way of tunicamycin application or PNGase F treatment in K562/ADR cells showed partial inhibition of biosynthesis and increased sensitivity to chemotherapeutic drugs in vitro. We targeted glycogene B3GNT8 and ST8SIA4, which were over-expressed in K562/ADR cells, and silenced the expression levels of two glycogenes after using RNA interference approach. The results showed that the silencing of B3GNT8 or ST8SIA4 in K562/ADR cells resulted in increased chemosensitivity to anti-tumor drugs. In conclusion, glycomic alterations are responsible for the overcoming multidrug resistance in human leukemia therapy and the N-linked oligosaccharides are associated with the drug resistance of cancer cells.

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Produktbeschreibung

Sigma-Aldrich
PNGase F aus Elizabethkingia meningoseptica, BioReagent, ≥95% (SDS-PAGE), for proteomics
Sigma-Aldrich
PNGase F aus Elizabethkingia meningoseptica, ready-to-use solution, recombinant, expressed in E. coli
Sigma-Aldrich
PNGase F aus Elizabethkingia miricola, buffered aqueous solution
Sigma-Aldrich
PNGase F aus Elizabethkingia meningoseptica, lyophilized powder, recombinant, expressed in E. coli
Sigma-Aldrich
PNGase F aus Elizabethkingia meningoseptica, recombinant, expressed in E. coli, set of 100 units nanomolar unit
Sigma-Aldrich
Glycopeptidase A from almonds, buffered aqueous glycerol solution, ≥0.05 unit/mL