Inducing-apoptosis effect of bortezomib on acute monocytic leukemia cell SHI-1 and its influence on expressions of Bcl2l12, Bcl-2 and Bax genes.
- Author:
Qi-Tian MU
1
;
Gui-Fang OUYANG
;
Yan-Ru LOU
;
Xiao-Pei CHEN
;
Ying LU
;
Wei LIANG
;
Yi ZHANG
;
Wei XU
Author Information
1. Ningbo First Hospital, Ningbo Laboratory of Stem Cell Transplantation, Ningbo 315010, Zhejiang Province, China. muqitian@163.com
- Publication Type:Journal Article
- MeSH:
Apoptosis;
drug effects;
Boronic Acids;
pharmacology;
Bortezomib;
Cell Line, Tumor;
Humans;
Leukemia, Monocytic, Acute;
genetics;
Muscle Proteins;
genetics;
Proto-Oncogene Proteins c-bcl-2;
genetics;
Pyrazines;
pharmacology;
RNA, Messenger;
bcl-2-Associated X Protein;
genetics
- From:
Journal of Experimental Hematology
2008;16(5):1016-1020
- CountryChina
- Language:Chinese
-
Abstract:
This study was aimed to explore the effect of bortezomib on proliferation and apoptosis of acute monocytic leukemic cells SHI-1 and the function of Bcl-2 gene family including Bcl2l12, Bcl-2 and Bax in its apoptosis. SHI-1 cells were cultured and treated with bortezomib of different concentrations for different time. MTT assay was used to detect the proliferation and apoptosis, Annexin-V staining, mitochondrial transmembrane potential (DeltaPsim) and DNA aga-rose gel electrophoresis were used to investigate apoptosis of SHI-1 cells. RT-PCR was used to analyze the levels of Bcl2l12, Bcl-2 and bax mRNA in SHI-1 cells treated with bortezomib for 0, 6, 12 and 24 hours. The results showed that bortezomib inhibited the proliferation of SHI-1 cells in time-and doze-dependent manners, the IC(50) at 24 and 48 hours were 54.13 nmol/L and 5.45 nmol/L respectively. Bortezomib could induce apoptosis of SHI-1 cells in time-dependent manner, increase expression of Annexin-V positive cells, decrease DeltaPsim of SHI-1 cells and result in DNA fragmentation and morphologic changes of apoptosis. RT-PCR showed that Bcl2l12 mRNA expression was up-regulated, bcl-2 mRNA expression was down-regulated and bax mRNA expression was not changed obviously. It is concluded that bortezomib inhibits the proliferation of SHI-1 and induces apoptosis in which Bcl2l12 and Bcl-2 gene can be ones of the main genes taking part in.
