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.
Article
in Zh
| WPRIM
| ID: wpr-229928
Responsible library:
WPRO
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>
Full text:
1
Database:
WPRIM
Main subject:
Pathology
/
Pharmacology
/
Tretinoin
/
Adenine
/
Leukemia, Promyelocytic, Acute
/
Cell Differentiation
/
Adenylyl Cyclases
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Phosphoric Diester Hydrolases
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Drug Resistance, Neoplasm
/
CD11b Antigen
Type of study:
Diagnostic_studies
Limits:
Humans
Language:
Zh
Journal:
Chinese Journal of Hematology
Year:
2004
Document type:
Article