Synergistic lethal effect of combined treatment of arsenic trioxide and aclacinomycin on human acute myeloid leukemia cell line KG-1a
10.3760/cma.j.issn.0253-3766.2017.04.004
- VernacularTitle: 三氧化二砷联合阿克拉霉素对急性髓系白血病KG-1a细胞的协同杀伤效应
- Author:
Yongbin YE
1
;
Xiaojun XU
1
;
Yanhong CHEN
1
;
Mingwan ZHANG
1
;
Dafa QIU
1
;
Ziwen GUO
1
;
Huiqing HE
1
Author Information
1. Department of Hematology, Zhongshan Hospital of Sun Yat-Sen University & Zhongshan People's Hospital, Zhongshan 528403, China
- Publication Type:Journal Article
- Keywords:
Arsenicum sublimatum;
Aclarubicin;
Leukemia, erythroblastic, acute;
Cytotoxicity, immunologic
- From:
Chinese Journal of Oncology
2017;39(4):256-262
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the synergistic lethal effect and mechanism of arsenic trioxide (ATO) and aclacinomycin (ACM) on human acute myeloid leukemia cell line KG-1a.
Methods:Colony-forming assay was used to detect the proliferation of KG-1a cells treated with different concentration of ATO and ACM. Compusyn software was used to analyze the synergistic effect of ATO and ACM. Flow cytometry and Wright's staining were used to analyze the apoptotic rate of KG-1a cells induced by combined treatment of ATO and ACM. Western blot was used to determine the expression of proteins associated with apoptosis.
Results:The cytotoxicity of arsenic trioxide or aclacinomycin alone was in a dose-dependent manner. Flow cytometry analysis showed that the apoptotic rate of KG-1a cells treated with both 0.4 μmol/L ATO and 10 nmol/L ACM was (34.5±3.1)%, significantly higher than (7.6±1.1)% of 0.4 μmol/L ATO treatment or (18.7±2.3) % of 10 nmol/L ACM treatment alone (P<0.05). The apoptotic rate of KG-1a cells treated with both 1.5 μmol/L ATO and 37.5 nmol/L ACM was (52.5±4.7)%, significantly higher than (19.1±3.2)% of 1.5 μmol/L ATO treatment or (27.7±2.2)% of 37.5 nmol/L ACM treatment alone (P<0.05). The apoptotic rate of KG-1a cells treated with both 3.0 μmol/L ATO and 75 nmol/L ACM was (61.3±4.5)%, significantly higher than (29.5±2.5)% of 3.0 μmol/L ATO treatment or (28.6±3.4) % of 75 nmol/L ACM treatment alone (P<0.05). In addition, the result of Wright's staining showed that combined treatment of ATO and ACM induced a more apparent phenotype of apoptosis when compared with single agent treatment. Compusyn software analysis showed that the combination index (CI) value of combined treatment group was less than 1, which indicated the synergistic effect of these two agents.
Conclusions:Combined treatment of ATO and ACM shows a synergistic lethal effect on human acute myeloid leukemia cell line KG-1a via activating the apoptotic pathway, which inhibits cell growth and induces apoptosis.
