Apoptotic Mechanism of Human Leukemia K562/A02 Cells Induced by Magnetic Ferroferric Oxide Nanoparti

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Background:Traditional Chinese medicine wogonin plays an important role in the treatment of leukemia.Recently,the application of drug-coated magnetic nanoparticles (MNPs) to increase water solubility of the drug and to enhance its chemotherapeutic efficiency has attracted much attention.Drugs coated with MNPs are becoming a promising way for better leukemia treatment.This study aimed to assess the possible molecular mechanisms of wogonin-coated MNP-Fe3O4 (Wog-MNPs-Fe3O4) as an antileukemia agent.Methods:After incubated for 48 h,the antiproliferative effects ofMNPs,wogonin,or Wog-MNPs-Fe3O4 on K562/A02 cells were determined by methyl thiazolyl tetrazolium (MTT) assay.The apoptotic rates of K562/A02 cells treated with either wogonin or Wog-MNPs-Fe3O4 were determined by flow cytometer (FCM) assay.The cell cycle arrest in K562/A02 cells was determined by FCM assay.The elementary molecular mechanisms of these phenomena were explored by West blot and reverse transcriptase polymerase chain reaction (RT-PCR).Results:With cell viabilities ranging from 98.76% to 101.43%,MNP-Fe3O4 was nontoxic to the cell line.Meanwhile,the wogonin and Wog-MNPs-Fe3O4 had little effects on normal human embryonic lung fibroblast cells.The cell viabilities of the Wog-MNPs-Fe3O4 group (28.64-68.36%) were significantly lower than those of the wogonin group (35.53-97.28%) in a dose-dependent manner in 48 h (P < 0.001).The apoptotic rate of K562/A02 cells was significantly improved in 50 μmol/L Wog-MNPs-Fe3O4 group (34.28%)compared with that in 50 μ,mol/L wogonin group (23.46%;P < 0.001).Compared with those of the 25 and 50 μ,mol/L wogonin groups,the ratios of G0/G1-phase K562/A02 cells were significantly higher in the 25 and 50 μmol/L Wog-MNPs-Fe3O4 groups (all P < 0.001).The mRNA and protein expression levels of the p21 and p27 in the K562/A02 cells were also significantly higher in the Wog-MNPs-Fe3O4 group compared with those of the wogonin group (all P < 0.001).Conclusions:This study demonstrated that MNPs were the effective drug delivery vehicles to deliver wogonin to the leukemia cells.Through increasing cells arrested at G0/G1-phase and inducing apoptosis of K562/A02 cells,MNPs could enhance the therapeutic effects ofwogonin on leukemia cells.These findings indicated that MNPs loaded with wogonin could provide a promising way for better leukemia treatment.
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