title: Glycomic alterations are associated with multidrug resistance in human leukemia.
abstract: 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.
authors.affiliation: College of Laboratory Medicine, Dalian Medical University, Dalian 116044, Liaoning Province, China.
authors.forename: Zhaohai
authors.initials: Z
authors.lastname: Zhang
authors.forename: Yongfu
authors.initials: Y
authors.lastname: Zhao
authors.forename: Lili
authors.initials: L
authors.lastname: Jiang
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Miao
authors.forename: Huimin
authors.initials: H
authors.lastname: Zhou
authors.forename: Li
authors.initials: L
authors.lastname: Jia
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005434:Flow Cytometry; D016650:Fluorescein-5-isothiocyanate / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D054794:Glycomics / Q000379:methods*; D006801:Humans; D020014:K562 Cells; D037102:Lectins / Q000378:metabolism; D007938:Leukemia / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics / Q000378:metabolism; D017239:Paclitaxel / Q000494:pharmacology; D043524:Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase / Q000378:metabolism; D011134:Polysaccharides / Q000096:biosynthesis* / Q000378:metabolism; D011485:Protein Binding; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012799:Sialyltransferases / Q000235:genetics / Q000378:metabolism; D014415:Tunicamycin / Q000494:pharmacology; D014750:Vincristine / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D037102:Lectins; D011134:Polysaccharides; D014415:Tunicamycin; D014750:Vincristine; D004317:Doxorubicin; C496333:B3GNT8 protein, human; D017351:N-Acetylglucosaminyltransferases; D012799:Sialyltransferases; C515117:ST8SIA4 protein, human; D043524:Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase; D016650:Fluorescein-5-isothiocyanate; D017239:Paclitaxel