Reversal effects of hyaluronan oligosaccharides on adriamycin resistance of K562/A02 cells.
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.
Cui
Xiangzhen
X
Institute of Biochemical and Biotechnological Drugs, School of Pharmaceutical Sciences, Shandong University, Shandong, China.
Zhou
Shuai
S
Xu
Huanli
H
Zhao
Ting
T
Liu
Aihua
A
Guo
Xueping
X
Wang
Fengshan
F
D000903:Antibiotics, Antineoplastic / Q000493:pharmacokinetics / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D004317:Doxorubicin / Q000493:pharmacokinetics / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D006820:Hyaluronic Acid / Q000031:analogs & derivatives* / Q000737:chemistry; D020014:K562 Cells; D015394:Molecular Structure; D009844:Oligosaccharides / Q000138:chemical synthesis* / Q000494:pharmacology*
D000903:Antibiotics, Antineoplastic; D009844:Oligosaccharides; D004317:Doxorubicin; D006820:Hyaluronic Acid