Mechanism of apoptosis of NB4 cells induced by arsenic trioxide and cyclooxygenase-2 expression.
- Author:
Da-Bing QIN
1
;
Jie-Ping CHEN
;
Sheng-Qi WANG
Author Information
1. Center of Hematology, Third Military Medical University Southwest Hospital, Chongqing 400038, China.
- Publication Type:Journal Article
- MeSH:
Apoptosis;
drug effects;
Arsenicals;
pharmacology;
Cell Line, Tumor;
Cyclooxygenase 2;
metabolism;
Humans;
Leukemia, Promyelocytic, Acute;
metabolism;
Membrane Potential, Mitochondrial;
Oxides;
pharmacology
- From:
Journal of Experimental Hematology
2011;19(3):648-651
- CountryChina
- Language:Chinese
-
Abstract:
Objective of this study was to investigate the changes of cyclooxygenase-2 expression and mitochondrial membrane potential in apoptotic NB4 cells induced by arsenic trioxide (As(2)O(3)). The morphological changes in apoptosis process of NB4 cells treated by arsenic trioxide were observed under immunofluorescence microscope and DNA electrophoresis method, and the apoptosis rate of NB4 cells and the variations of mitochondrial membrane potential were detected by flow cytometry. Furthermore, the variations of expression level of cyclooxygenase-2 protein were analyzed by using Western blot method. The results indicated that after NB4 cells were treated with 2 µmol/L As(2)O(3) for 48 hours, some variations of NB4 cells were observed, such as pyknosis, chromatin segmentation, even fragmentation. Meanwhile, the typical DNA Ladder phenomenon was observed. The apoptosis rate of NB4 cells treated with 3 µmol/L As(2)O(3) for 48 hours was 33.34%, Furthermore the apoptosis rate of NB4 cells was enhanced along with the increase of concentration of As(2)O(3). After NB4 cells were treated with 0.5, 1, 2, 4 and 8 µmol/L As(2)O(3) for 48 hours, the mitochondrial membrane potential decreased by 12.8%, 21.6%, 66.9%, 83.7% and 83.8% respectively. The Western blot detection results showed that the expression level of cyclooxygenase-2 protein in NB4 cells was lower than that in control cells and decreased along with the rise of As(2)O(3) concentration, then the negative dose-dependent manner was observed between these 2 groups. It is concluded that As(2)O(3) can effectively induce NB4 cell apoptosis, and the dose-dependent manner existed in certain extent of concentrations. The decrease of mitochondrial membrane potential may be related with NB4 cell apoptosis induced by As(2)O(3). Cyclooxygenase-2 participates in the process of NB4 cell apoptosis induced by As(2)O(3).
