Curcumin synergistically augments bcr/abl phosphorothioate antisense oligonucleotides to inhibit growth of chronic myelogenous leukemia cells  

作　　者：Kun-zhong ZHANG Jian-hua XU Xiu-wang HUANG Li-xian WU Yu SU Yuan-zhong CHEN 

机构地区：[1]Institute of Clinical Pharmacology, School of Pharmacy, Fujian Medical University, Fujian 350004, China [2]Fujian Institute of Hematology, Fujian 350004,China

出　　处：《Acta Pharmacologica Sinica》2007年第1期105-110,共6页中国药理学报（英文版）

基　　金：Project supported by the National Natural Science Foundation of China(No 30171158 and No 30472187);the Natural Science Foundation of Fujian Province,China(No C992001).

摘　　要：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 P210^bcr/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 P210^bcr/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 P210^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 the cell growth of K562. The synergistic growth inhibition was mediated through different mechanisms that involved the inhibition of P210^bcr/abl.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 P210^bcr/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 P210^bcr/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 P210^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 the cell growth of K562. The synergistic growth inhibition was mediated through different mechanisms that involved the inhibition of P210^bcr/abl.

关 键 词：combination drug therapy CURCUMIN ablgenes  antisense oligonucleotides chronicmyelogenous leukemia bcr-abl fusionproteins 

分 类 号：R733.72[医药卫生—肿瘤]