Document Detail

Reversal effects of hyaluronan oligosaccharides on adriamycin resistance of K562/A02 cells.
MedLine Citation:
PMID:  19606017     Owner:  NLM     Status:  MEDLINE    
As the interaction of hyaluronan (HA) with its receptor CD44 contributes to multidrug resistance (MDR) of tumor cells, HA oligosaccharides (o-HAs), as HA antagonists, may be useful to reverse the MDR. The objective of this study was to investigate the reversal effects of four o-HAs, including 4 saccharide residue (o-HA4), 6 saccharide residue (o-HA6), 8 saccharide residue (o-HA8), and 10 saccharide residue (o-HA10) fragments, on adriamycin (ADR)-resistant K562/A02 cells. The four o-HAs were prepared by digesting the native high molecular weight HA with hyaluronidase and gel filtration chromatography. 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay was used to assess the cytotoxicity of the four o-HAs and/or ADR on K562/A02 and K562 cells. The intracellular accumulation of ADR in K562/A02 cells was measured by flow cytometry. By comparing the IC50 (concentration resulting in 50% inhibition of cell growth) of ADR with K562/A02 cells in the presence and absence of a series of different concentrations of o-HAs, the reversal folds of the four o-HAs were calculated. The reversal folds of o-HA4, o-HA6, o-HA8, and o-HA10 were 2.04, 2.05, 1.91, and 1.84, respectively. After o-HA4, o-HA6, o-HA8, and o-HA10 treatment, the intracellular amounts of ADR were increased to 3.90, 3.92, 3.76, and 3.39 times, respectively. Shorter o-HAs (o-HA4 and o-HA6) showed stronger reversal effects than longer o-HAs (o-HA8 and o-HA10). In conclusion, the results showed that the four o-HAs could effectively reverse the ADR resistance of K562/A02 cells by increasing the intracellular accumulation of ADR. O-HAs may be used as MDR reversal drugs to increase the effectiveness of chemotherapy.
Xiangzhen Cui; Shuai Zhou; Huanli Xu; Ting Zhao; Aihua Liu; Xueping Guo; Fengshan Wang
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Anti-cancer drugs     Volume:  20     ISSN:  1473-5741     ISO Abbreviation:  Anticancer Drugs     Publication Date:  2009 Oct 
Date Detail:
Created Date:  2009-09-03     Completed Date:  2009-12-31     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9100823     Medline TA:  Anticancer Drugs     Country:  England    
Other Details:
Languages:  eng     Pagination:  800-6     Citation Subset:  IM    
Institute of Biochemical and Biotechnological Drugs, School of Pharmaceutical Sciences, Shandong University, Shandong, China.
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MeSH Terms
Antibiotics, Antineoplastic / pharmacokinetics,  pharmacology
Cell Proliferation / drug effects
Doxorubicin / pharmacokinetics,  pharmacology*
Drug Resistance, Neoplasm / drug effects*
Drug Screening Assays, Antitumor
Hyaluronic Acid / analogs & derivatives*,  chemistry
K562 Cells
Molecular Structure
Oligosaccharides / chemical synthesis*,  pharmacology*
Reg. No./Substance:
0/Antibiotics, Antineoplastic; 0/Oligosaccharides; 23214-92-8/Doxorubicin; 9004-61-9/Hyaluronic Acid

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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