[Experimental study of the enhancement effect of aminopeptidase N inhibitor ubenimex on the differentiation induction activity of all-trans-retinoic acid in acute promyelocytic leukemia cells and its mechanism].
OBJECTIVE
To investigate the effect of aminopeptidase N inhibitor ubenimex on differentiation induction of all-trans-retinoic acid (ATRA) in acute promyelocytic leukemia (APL) cells and its mechanism.


METHODS
The expression of CD11b was analyzed by flow cytometry and nitroblue-tetrazolium (NBT) reduction assay was performed to determine the cell differentiation of APL cells. The expressions of c-Myc, ERK1/2, p38MAPK protein and the phosphorylation of ERK1/2, p38MAPK protein in NB4 cells were detected by Western blot assay.


RESULTS
Ubenimex alone induced no significant changes in NBT reduction activity and CD11b expression but potentiated the differentiation induction activity of ATRA in APL cells. 100 microg/ml of ubenimex could enhance the NBT reduction activity induced by 10 nmol/L of ATRA, intensify the down-regulation of c-Myc protein expression and inhibit the phosphorylation of p38MAPK protein induced by 10 nmol/L of ATRA in NB4 cells.


CONCLUSIONS
Ubenimex could potentiate ATRA induced differentiation in APL cells, which may be correlated with the inhibition of p38 MAPK protein phosphorylation and regulation of c-Myc protein expression.
Qian
Xi-Jun
XJ
Department of Hematology, First Affiliated Hospital, Medical College of Zhejiang University, Hangzhou 310003, China.
Lin
Mao-Fang
MF
D000626:Aminopeptidases / Q000037:antagonists & inhibitors; D002454:Cell Differentiation / Q000187:drug effects*; D004357:Drug Synergism; D005434:Flow Cytometry; D006801:Humans; D066298:In Vitro Techniques; D007930:Leucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015473:Leukemia, Promyelocytic, Acute / Q000473:pathology*; D014212:Tretinoin / Q000494:pharmacology*
D014212:Tretinoin; D000626:Aminopeptidases; D007930:Leucine; C012211:ubenimex