Activation of adenylate cyclase influences the sensitivity of acute promyelocytic leukemia cell lines to ATRA / 中华血液学杂志
Chinese Journal of Hematology
;
(12): 675-678, 2004.
Artigo
em Chinês
| WPRIM
| ID: wpr-229928
ABSTRACT
<p><b>OBJECTIVE</b>To explore the molecular mechanism of APL cell resistance to ATRA.</p><p><b>METHODS</b>The ATRA sensitive and resistant APL cell lines, NB4 and NB4-R1, were used as in vitro models. The effects of specific inhibitors and activators of adenylate cyclase (AC) and phosphodiesterase (PDE) on ATRA-induced differentiation was evaluated by cell morphology, cell surface antigen expression and nitroblue-tetrazolium (NBT) reduction assays.</p><p><b>RESULTS</b>SQ22536, a specific antagonist of AC, could dramatically block ATRA-induced NB4 cell differentiation. When ATRA + SQ22536 group compared with ATRA group, the positivity of CD11b decreased from (95.9 +/- 2.5)% to (60.3 +/- 7.1)%, while the A(540) in NBT reduction assay decreased from 0.585 +/- 0.092 to 0.170 +/- 0.028 (P < 0.05). Forskolin, an agonist of AC, could overcome the resistance of NB4-R1 cells to ATRA. When ATRA + forskolin group compared with ATRA group, the positivity of CD11b increased from (34.3 +/- 5.3)% to (94.6 +/- 2.4)%, while the A(540) in NBT reduction assay increased from 0.110 +/- 0.028 to 0.395 +/- 0.049 (P < 0.05). In contrast, the specific antagonist and agonist of PDE, 3-isobutyl-1-methylxanthine (IBMX) and calmodulin, exerted little impact on ATRA treatment.</p><p><b>CONCLUSIONS</b>The defaults in the initiation of AC activation may contribute to the resistance to ATRA in some APL cells.</p>
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Patologia
/
Farmacologia
/
Tretinoína
/
Adenina
/
Leucemia Promielocítica Aguda
/
Diferenciação Celular
/
Adenilil Ciclases
/
Diester Fosfórico Hidrolases
/
Resistencia a Medicamentos Antineoplásicos
/
Antígeno CD11b
Tipo de estudo:
Estudo diagnóstico
Limite:
Humanos
Idioma:
Chinês
Revista:
Chinese Journal of Hematology
Ano de publicação:
2004
Tipo de documento:
Artigo
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