Gene Expression Profile of Apoptosis in Leukemia Cells Induced by Hsp90 Selective inhibitor 17-AAG.
- Author:
Na-Na WANG
1
;
Zhi-Heng LI
1
;
Yan-Fang TAO
1
;
Li-Xiao XU
1
;
Jian PAN
1
;
Shao-Yan HU
2
Author Information
- Publication Type:Journal Article
- MeSH: Apoptosis; Benzoquinones; pharmacology; Caspase 3; metabolism; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Down-Regulation; HL-60 Cells; HSP90 Heat-Shock Proteins; antagonists & inhibitors; Humans; Lactams, Macrocyclic; pharmacology; Leukemia; metabolism; Poly(ADP-ribose) Polymerases; metabolism; Real-Time Polymerase Chain Reaction; Signal Transduction; Transcriptome
- From: Journal of Experimental Hematology 2016;24(3):672-680
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo investigate the apoptotic effects of Hsp90 selective inhibitor 17-AAG on human leukemia HL-60 and NB4 cells and analyse its possible mechanism.
METHODSCCK-8 assay was used to quantify the growth inhibition of cells after exposure to 17-AAG for 24 hours. Flow cytometrve with annexin V/propidium iodide staining was used to detect apoptosis of leukemia cells. Then Western blot was used to detect the activation of apoptosis related protein caspase-3 and PARP level. Gene expression profile of NB4 cells treated with 17-AAG was analyzed with real-time PCR arrays.
RESULTSThe inhibition of leukemia cell proliferation displayed a dose-dependent manner. Annexin V assay, cell cycle analysis and activation of PARP demonstrate that 17-AAG induced apoptosis leukemia cells. Real-time PCR array analysis showed that expression of 56 genes significantly up-regulated and expression of 23 genes were significantly down-regulated after 17-AAG treatment.
CONCLUSIONThe 17-AAG can inhibit the proliferation and induce the apoptosis of leukemia cells. After leukemia cells are treated with 17-AAG, the significant changes of apoptosis-related genes occured, and the cell apoptosis occurs via activating apoptosis related signaling pathway.
