Abstract
Aim:
To investigate the growth inhibition effect of the combination of bcr/abl phosphorothioate antisense oligonucleotides (PS-ASODN) and curcumin (cur), and the possible mechanisms of cur on the chronic myelogenous leukemia cell line K562.
Methods:
The K562 cell line was used as a P210bcr/abl-positive cell model in vitro and was exposed to different concentrations of PS-ASODN (0-20 μmol/L), cur (0-20 μmol/L), or a combination of both. Growth inhibition and apoptosis of K562 cells were assessed by MTT assay and AO/EB fluorescent staining, respectively. The expression levels of P210bcr/abl, NF-κB and heat shock protein 90 (Hsp90) were assessed by Western blot.
Results:
Exposure to cur (5-20 μmol/L) and PS-ASODN (5-20 μmol/L) resulted in a synergistic inhibitory effect on cell growth. Growth inhibition was associated with the inhibition of the proliferation and induction of apoptosis. Western blot analysis showed that the drugs synergistically downregulated the level of P210bcr/abl and NF-κB. Cur downregulated Hsp90, whereas no synergism was observed when cur was combined with PS-ASODN.
Conclusion:
PS-ASODN and cur exhibited a synergistic inhibitory effect on the cell growth of K562. The synergistic growth inhibition was mediated through different mechanisms that involved the inhibition of P210bcr/abl.
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Project supported by the National Natural Science Foundation of China (No 30171158 and No 30472187), and the Natural Science Foundation of Fujian Province, China (No C992001).
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Zhang, Kz., Xu, Jh., Huang, Xw. et al. Curcumin synergistically augments bcr/abl phosphorothioate antisense oligonucleotides to inhibit growth of chronic myelogenous leukemia cells. Acta Pharmacol Sin 28, 105–110 (2007). https://doi.org/10.1111/j.1745-7254.2007.00471.x
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DOI: https://doi.org/10.1111/j.1745-7254.2007.00471.x
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