Arsenic trioxide inhibits cell growth in imatinib-resistant bcr-abl mutant cell lines in vitro / 中华血液学杂志
Chinese Journal of Hematology
; (12): 13-17, 2009.
Article
en Zh
| WPRIM
| ID: wpr-314519
Biblioteca responsable:
WPRO
ABSTRACT
<p><b>OBJECTIVE</b>To explore the effect of arsenic trioxide (As2O3) on the growth inhibition of imatinib (IM)-resistant bcr-abl mutant cell lines in vitro.</p><p><b>METHODS</b>Cell growth of one IM-sensitive cell line, 32Dp210 and 15 IM-resistant cell lines including T315I and other 14 bcr-abl mutants were detected by MTT assay after treatment with IM and As2O3. The cell lines with 5 frequently observed mutants in CML patients were analyzed for apoptosis by flow cytometry with Annexin V and PI staining as well as the expression of bcr-abl fusion protein, phosphorylated CRKL protein and apoptosis-related proteins by Western blot.</p><p><b>RESULTS</b>The fifty percent inhibition concentration (IC50) values of As2O3 for 15 IM-resistant cell lines were 2.6-5.3 fold lower than that for IM-sensitive cell line. For the 5 bcr-abl mutants frequently happened in CML patients, As2O3 significantly inhibited the expression of bcr-abl fusion protein and phosphorylated CRKL and induced apoptosis in a dose-dependent manner as compared with that for 32Dp210. Coincidently, the cell apoptosis was induced through caspase-3, 8 and 9 pathways.</p><p><b>CONCLUSION</b>As2O3 remarkably inhibits cell growth and induces apoptosis of IM-resistant bcr-abl mutant cell lines in vitro, suggesting that it might be a potential therapeutic agent for IM-resistant CML patients.</p>
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Asunto principal:
Óxidos
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Farmacología
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Piperazinas
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Arsenicales
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Pirimidinas
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Benzamidas
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Proteínas Nucleares
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Proteínas de Fusión bcr-abl
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Apoptosis
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Resistencia a Antineoplásicos
Límite:
Humans
Idioma:
Zh
Revista:
Chinese Journal of Hematology
Año:
2009
Tipo del documento:
Article