In vitro study of the effects of arsenic trioxide combined with 8-CPT-cAMP on differentiation induction in retinoic acid resistant acute promyelocytic leukemia cells.
- Author:
Qi ZHU
1
;
Yun YU
;
Pei-min JIA
;
Xun CAI
;
Sai-juan CHEN
;
Zhu CHEN
;
Zhen-yi WANG
;
Jian-hua TONG
Author Information
- Publication Type:Journal Article
- MeSH: Antineoplastic Agents; pharmacology; Arsenicals; pharmacology; Cell Differentiation; drug effects; Cell Line, Tumor; Cyclic AMP; analogs & derivatives; pharmacology; Dose-Response Relationship, Drug; Drug Resistance, Neoplasm; Drug Synergism; Humans; Leukemia, Promyelocytic, Acute; pathology; Oxides; pharmacology; Thionucleotides; pharmacology; Tretinoin; pharmacology
- From: Chinese Journal of Hematology 2003;24(1):6-9
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo investigate the potential effects of arsenic trioxide (As(2)O(3)) combined with 8-(4-chlorophenylthio) adenosine 3', 5'-cyclic monophosphate (8-CPT-cAMP) on the retinoic acid (RA)-resistant acute promyelocytic leukemia (APL) cells.
METHODSThe RA resistant APL cell lines NB4-R1 and NB4-R2 were used as in vitro models. The effect of As(2)O(3) and/or 8-CPT-cAMP was evaluated according to cellular morphology, cell surface antigen and nitroblue-tetrazolium (NBT) assay. Meanwhile, immunofluorescence analysis and Western blot assay were used to detect the degradation of PML-RAR alpha fusion protein and the change of several key cell cycle regulatory proteins in these cells before and after the treatment.
RESULTSLow dose of As(2)O(3) (0.25 micromol/L) synergized with 8-CPT-cAMP (200 micromol/L) in inducing differentiation of NB4-R1 and NB4-R2 cells, while neither of these two drugs alone could induce differentiation of these cells. In addition, 8-CPT-cAMP was able to inhibit the cell growth by modulating the expression of some important cell cycle regulators and to facilitate the As(2)O(3)-mediated degradation of PML-RAR alpha fusion protein.
CONCLUSIONSAs(2)O(3) combined with 8-CPT-cAMP could induce differentiation of RA-resistant APL cells.
