Increase of leukemia cell apoptosis through the down-regulation of silencer of death domains by Paclitaxel
10.3760/cma.j.issn.2095-428X.2014.11.017
- VernacularTitle:紫杉醇下调死亡结构域沉默子表达促进白血病细胞凋亡新机制研究
- Author:
Hongfang TAO
;
Jianlin FANG
;
Yuansheng LIU
;
Yongzhong SU
;
Feiheng CHEN
;
Huijun LI
- Publication Type:Journal Article
- Keywords:
Paclitaxel;
Silencer of death domains;
Molecular targetting;
Leukemia
- From:
Chinese Journal of Applied Clinical Pediatrics
2014;29(11):862-865
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the signaling pathway of apoptosis induced by Paclitaxel (PTX) in leukemia cells and the chemosensitizing effect of adding short hairpin RNA(shRNA) on PTX,which targets the silencer of death domains(SODD).Methods After being treated with PTX,the expressions of SODD,B-cell lymphoma/leukemia-2 (Bcl-2),nuclear factor kappa B (NF-κB) and Caspase-3 proteins in Jurkat cells were determined by Western blot ;the shRNA-SODD vectors were constructed and transfected into Jurkat cells by electroporation,and then G418 was used to select the stable tranfected cell line expressing the shRNA-SODD recombinant plasmids.The incidence of cell apoptosis induced by PTX was determined by flow cytometry labeled with propidium iodide.Results During the process of inducing apoptosis of Jurkat cells,PTX could significantly down-regulate the expressions of SODD and Bcl-2 proteins,degrade Caspase-3 and activate NF-κB.The apoptotic sensibility of Jurkat cells transfected with shRNA-SODD to PTX was significantly increased compared with the control group,and the difference was statistically significant (F =10.35,P ＜ 0.05).Conclusions PTX can effectively induce apoptosis of Jurkat cells.Perhaps,SODD/Bcl-2 represents a specific apoptotic signaling pathway of PTX in leukemia cells and this apoptotic signaling pathway is Caspase-3-dependent,in which the function of NF-κB is to modulate the correlative apoptotic factors.Inhibiting the expression of SODD through transfecting shRNA-SODD vectors can significantly increase the apoptotic sensibility of leukemia cells to PTX.
