Study on cytotoxicity of Gemtuzumab Ozogamicin in acute myeloid leukemia and its relationship with expression level of CD33 #br#
WANG Zhenzhen1 LI Weijing2
1.Department of Hematopathology, the Second Hospital of Hebei Medical University, Hebei Province, Shijiazhuang 050000, China;
2.Department of Hematopathology, the Fourth Hospital of Hebei Medical University, Heibei Province, Shijiazhuang 050011, China
Abstract：Objective To explore the relationship between the cytotoxicity of Gemtuzumab Ozogamicin (GO) on acute myeloid leukemia (AML) cells and the expression level of CD33 and the mechanism of action. Methods Human myeloid OCI-AML3 and KG-1a cells were transfected with lentivirus containing CD33 plasmid, then the cells were divided into CD33 high expression group and CD33 low expression group according to CD33 expression level. Both groups were treated with 15 μg/L GO, and then the survival rate of cells in the two groups was determined by MTT assay. OCI-AML3 cells were treated with different concentrations of GO (0, 5, 10, 15 μg/L), and then the expression levels of apoptosis-related proteins Bcl-2, cleaved caspase 3, and caspase 3 were detected by Western blot. Results After transfection, the expression levels of CD33 on OCI-AML3 and KG-1a cells were higher than that before transfection, and the differences were statistically significant (P ＜ 0.05). After the same concentration of GO treatment, the survival rates of OCI-AML3 and KG-1a cells in CD33 high expression group were lower than those in CD33 low expression group, the differences were statistically significant (P ＜ 0.05). When GO concentration was 5, 10, 15 μg/L, the Bcl-2 level of OCI-AML3 cells was lower than those when GO concentration was 0, and cleaved-caspase 3 and caspase 3 levels were higher than those when GO concentration was 0. When GO concentration was 10, 15 μg/L, the Bcl-2 level of OCI-AML3 cells was lower than that when GO concentration was 5 μg/L, and cleaved-caspase 3 and caspase 3 levels were higher than those when GO concentration was 5 μg/L. When GO concentration was 15 μg/L, the Bcl-2 level of OCI-AML3 cells was lower than those when GO concentration was 10 μg/L, and cleaved-caspase 3 and caspase 3 levels were higher than those when GO concentration was 10 μg/L, the differences were statistically significant (P ＜ 0.05). Conclusion GO has enhanced inhibitory effect on proliferation of human myeloid cells with high CD33 expression, and can promote apoptosis of AML cells by regulating the expression of apoptotic proteins.
王真真1 李炜静2. 奥佐米星对急性髓细胞性白血病的细胞毒性及其与CD33表达水平的关系研究[J]. 中国医药导报, 2022, 19(7): 15-18.
WANG Zhenzhen1 LI Weijing2. Study on cytotoxicity of Gemtuzumab Ozogamicin in acute myeloid leukemia and its relationship with expression level of CD33 #br#. 中国医药导报, 2022, 19(7): 15-18.
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