|Potentiation of arsenic trioxide-induced apoptosis by retinoic acid in retinoic acid sensitive and resistant HL-60 myeloid leukemia cells|
|关键词||arsenic trioxide (AS(2)O(3)) retinoic acid(RA) HL-60 cells|
|刊名||CHINESE MEDICAL JOURNAL|
|WOS标题词||Science & Technology|
|类目[WOS]||Medicine, General & Internal|
|研究领域[WOS]||General & Internal Medicine|
|关键词[WOS]||ACUTE PROMYELOCYTIC LEUKEMIA ; PML ; EXPRESSION ; AS2O3 ; ALPHA|
Objective To study the effect of arsenic trioxide (As2O3) on non-APL acute myeloid leukemia (AML) cells and the interreactive effect between retinoic acid (RA) and AS(2)O(3)
Methods RA-sensitive (S) and RA-resistant (R) HL-60 non-APL AML cells were used as an in vitro model. Cell number and trypan blue were used to observe cell growth and survival. Apoptosis was determined by morphological changes, using a DNA laddering assay, terminal deoxynucleotidyl transferase (TdT) fragment end labeling assay and a flow cytometry assay.
Results As2O3 induced apoptosis in both HL-60S and HL-60R cells, As2O3-induced apoptosis was both time- and concentration-dependent in a therapeutically-achievable As(O0)3 range (0.25 - 4.0 mu mol/l). Both all-trans retinoic acid (ATRA) and 9-cis retinoic acid (9cRA) potentiated As2O3-induced apoptosis, as measured by quantitative TdT fragment end labeling and flow cytometry assays in both HL-60S and HL-60R cells ( P < 0.05, for all RA + As2O3 combinations vs As2O3 alone in both sublines).
Conclusions As2O3 may inhibit the growth of non-APL AML cells by promoting programmed cell death. RA can potentiate As2O3-induced apoptosis even in RA-resistant HL-60 cells in which the classical ATRA response pathway is repressed owing to a homozygous inactivating mutation in the retinoic acid receptor proportional to. As2O3 can have clinical activity in non-APL cases of AML and the enhanced activity might result from the combined As2O3-RA therapy.
|作者单位||Beijing Med Univ, Peoples Hosp, Inst Hematol, Beijing 100044, Peoples R China|
|Huang, XJ. Potentiation of arsenic trioxide-induced apoptosis by retinoic acid in retinoic acid sensitive and resistant HL-60 myeloid leukemia cells[J]. CHINESE MEDICAL JOURNAL,2000,113(6):498-501.|
|APA||Huang, XJ.(2000).Potentiation of arsenic trioxide-induced apoptosis by retinoic acid in retinoic acid sensitive and resistant HL-60 myeloid leukemia cells.CHINESE MEDICAL JOURNAL,113(6),498-501.|
|MLA||Huang, XJ."Potentiation of arsenic trioxide-induced apoptosis by retinoic acid in retinoic acid sensitive and resistant HL-60 myeloid leukemia cells".CHINESE MEDICAL JOURNAL 113.6(2000):498-501.|