In vitro study of the effects of arsenic trioxide combined with 8-CPT-cAMP on differentiation induction in retinoic acid resistant acute promyelocytic leukemia cells / 中华血液学杂志
Chinese Journal of Hematology
; (12): 6-9, 2003.
Article
em Zh
| WPRIM
| ID: wpr-261369
Biblioteca responsável:
WPRO
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the potential effects of arsenic trioxide (As(2)O(3)) combined with 8-(4-chlorophenylthio) adenosine 3', 5'-cyclic monophosphate (8-CPT-cAMP) on the retinoic acid (RA)-resistant acute promyelocytic leukemia (APL) cells.</p><p><b>METHODS</b>The RA resistant APL cell lines NB4-R1 and NB4-R2 were used as in vitro models. The effect of As(2)O(3) and/or 8-CPT-cAMP was evaluated according to cellular morphology, cell surface antigen and nitroblue-tetrazolium (NBT) assay. Meanwhile, immunofluorescence analysis and Western blot assay were used to detect the degradation of PML-RAR alpha fusion protein and the change of several key cell cycle regulatory proteins in these cells before and after the treatment.</p><p><b>RESULTS</b>Low dose of As(2)O(3) (0.25 micromol/L) synergized with 8-CPT-cAMP (200 micromol/L) in inducing differentiation of NB4-R1 and NB4-R2 cells, while neither of these two drugs alone could induce differentiation of these cells. In addition, 8-CPT-cAMP was able to inhibit the cell growth by modulating the expression of some important cell cycle regulators and to facilitate the As(2)O(3)-mediated degradation of PML-RAR alpha fusion protein.</p><p><b>CONCLUSIONS</b>As(2)O(3) combined with 8-CPT-cAMP could induce differentiation of RA-resistant APL cells.</p>
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Base de dados:
WPRIM
Assunto principal:
Óxidos
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Patologia
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Farmacologia
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Arsenicais
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Tionucleotídeos
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Tretinoína
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Leucemia Promielocítica Aguda
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Diferenciação Celular
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AMP Cíclico
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Resistencia a Medicamentos Antineoplásicos
Limite:
Humans
Idioma:
Zh
Revista:
Chinese Journal of Hematology
Ano de publicação:
2003
Tipo de documento:
Article