Curcumin synergistically augments bcr/abl phosphorothioate antisense oligonucleotides to inhibit gro

来源 :Acta Pharmacologica Sinica | 被引量 : 0次 | 上传用户:chendegeng1234
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Aim:To investigate the growth inhibition effect of the combination of bcr/ablphosphorothioate antisense oligonucleotides(PS-ASODN)and curcumin(cur),and the possible mechanisms of cur on the chronic myelogenous leukemia cell lineK562.Methods:The K562 cell line was used as a P210~(bcr/abl)-positive cell model invitro 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 ofK562 cells were assessed by MTT assay and AO/EB fluorescent staining,respec-tively.The expression levels of P210~(bcr/abl),NF-κ3 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 in-duction of apoptosis.Western blot analysis showed that the drugs synergisti-cally downregulated the level ofP210~(bcr/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 thecell growth of K562.The synergistic growth inhibition was mediated throughdifferent mechanisms that involved the inhibition of P210~(bcr/abl). Aim: To investigate the growth inhibition effect of the combination of bcr / ablphosphorothioate 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 P210 ~ (bcr / abl) -positive cell model invitro and was exposed to different concentrations of PS-ASODN (0-20 μmol / L), cur (0-20 μmol / L), or a combination of both. inhibition and apoptosis of K562 cells were assessed by MTT assay and AO / EB fluorescent staining, respec- tively.The expression levels of P210 ~ (bcr / abl), NF-κ3 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 in-duction of apoptosis. Western blot analysis showed that the drugs synergisti-cally downregulated the level ofP210 ~ (bcr / abl) and NF-κB.Cur down regulated Hsp90, and without synergism was observed when cur was combined with PS-ASODN. Conlusion: PS-ASODN and cur promoted a synergistic inhibitory effect on the cell growth of K562.The synergistic growth inhibition was mediated through different mechanisms that involved the inhibition of P210 ~ (bcr / abl).
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