[Effects of arsenic trioxide and ATRA on PLZF-RARalpha-positive U937 leukemic cells].
OBJECTIVE
To investigate effects of arsenic trioxide (As(2)O(3)) and alltrans retinoic acid (ATRA) on PLZF-RARalpha-positive cells.


METHODS
PLZF-RARalpha-positive U937 cells (U937/PLZF) were used as an in vitro model. The change of cell morphology was observed by Wright-Giemsa staining. Cell growth and proliferation were detected by methyl thiazolyl tetrazolium(MTT) assay. Cell cycle distribution and expression of cell membrane surface differentiation-related antigens (such as CD11b, CD64 and CD14) were determined by flow cytometry assay. Expression of PLZF was analyzed by immunofluorescence. Functional differentiation was reflected by nitroblue tetrazolium(NBT) reduction ability and cytochemistry staining.


RESULTS
While U937/PLZF cells were incubated in tetracycline-withdrawn medium, the expression of PLZF-RARalpha; protein increased. After treated with As(2)O(3) (0.5 micromol/L) and ATRA (1 mumol/L), U937/PLZF cells presented some changes such as decreased nuclear/cytoplasm ratio, and partial disappearance of nucleoli, suggesting a certain degree of morphological differentiation. The cell growth and proliferation were inhibited in a dose- and time-dependent manner. The proportion of cells in S phage was decreased and CD11b level was increased. The expression of PLZF relocated in treated cells. However, no significant difference in NBT assay and cytochemistry staining was documented with the combination therapy.


CONCLUSIONS
The combination of As(2)O(3) with ATRA can cause a slight tendency to morphological differentiation but is insufficient to induce functional differentiation of PLZF-RARalpha positive U937 leukemia cells.
Chen
Si-yu
SY
Department of Oncology, Xinhua Hospital, Shanghai Jiaotong University, Shanghai 200092, China.
Ma
Li-heng
LH
Dong
Ying
Y
Guo
Wei-jian
WJ
Wang
Zhen-yi
ZY
D015703:Antigens, CD / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism*; D007938:Leukemia / Q000378:metabolism / Q000473:pathology*; D009580:Nitroblue Tetrazolium / Q000378:metabolism; D010084:Oxidation-Reduction; D010087:Oxides / Q000494:pharmacology*; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D018168:Receptors, Retinoic Acid / Q000378:metabolism*; D000072482:Retinoic Acid Receptor alpha; D013752:Tetracycline / Q000494:pharmacology; D014212:Tretinoin / Q000494:pharmacology*; D020298:U937 Cells