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Artigo em Chinês | WPRIM | ID: wpr-231564

RESUMO

<p><b>OBJECTIVE</b>To study the effect of antisense oligonucleotide targeted on miRNA-21 (AMO-miR-21) for enhancing the arsenic trioxide (As2O3) sensitivity of leukemic K562 cells and its possible acting mechanism.</p><p><b>METHODS</b>Chemosynthetic AMO-miR-21 was transfected to K562 cells using Lipofectamine TM 2000. The inhibitory effects of As2O3 and AMO-miR-21, used singly or in combining, on cell proliferation were detected by MTT, their inhibition rate and IC50 were calculated. Cell cycle and apoptosis were assessed with PI stain; expression of miRNA-21 in cells was detected quantitatively by real-time PCR, and the potential target gene PDCD, protein expression was detected by immuno-fluorimetry.</p><p><b>RESULTS</b>Used in combining with AMO-miR-21, the IC50 of As2O3, could be lowered from 2.1 micromol/L to 1.23 micromol/L, and the sensitivity of cells to As2O3 increased to 1.78-fold; with the amount of apoptotic cells increased significantly. Transfection with AMO-miR-21 alone could downregulate the expression of miRNA-21 in cells (P < 0.01), and up-regulate PDCD, protein expression level significantly.</p><p><b>CONCLUSIONS</b>Combined use of AMO-miR-21 and As2O3 could increase the sensitivity of K562 cells to As2O3, which provides a novel potential approach for treatment of leukemia. AMO-miR-21 realizes it anti-tumor action by way of targeted inhibition on miRNA-21, and further up-regulates the expression of anti-tumor gene PDCD4.</p>


Assuntos
Humanos , Antineoplásicos , Farmacologia , Proteínas Reguladoras de Apoptose , Metabolismo , Arsenicais , Farmacologia , Regulação Leucêmica da Expressão Gênica , Células K562 , MicroRNAs , Oligonucleotídeos Antissenso , Farmacologia , Óxidos , Farmacologia , Proteínas de Ligação a RNA , Metabolismo , Transfecção
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