Effect of ADAM10 Inhibitor GI254023X on Proliferation and Apoptosis of Multiple Myeloma H929 Cells and Its Possible Mechanisms.
- Author:
Li-Li CHEN
1
,
2
;
Guo-Qin FAN
1
;
Zhi-Yao ZHANG
1
;
Bing-Yun ZHANG
1
;
Zhi-Ling YAN
1
;
Hu-Jun LI
1
;
Jian-Ping LUO
1
;
Chong CHEN
1
;
Yao YAO
1
;
Kai-Lin XU
1
;
Zhen-Yu LI
1
;
Author Information
- Publication Type:Journal Article
- MeSH: ADAM Proteins; ADAM10 Protein; Amyloid Precursor Protein Secretases; Apoptosis; Cell Line, Tumor; Cell Proliferation; Dipeptides; Down-Regulation; Humans; Hydroxamic Acids; Membrane Proteins; Multiple Myeloma; Receptor, Notch1
- From: Journal of Experimental Hematology 2015;23(6):1628-1632
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo investigate the effect of ADAM10 inhibitor GI254023X on the proliferation and apoptosis of multiple myeloma H929 cell line and its mechanisms.
METHODSH929 cells were treated with different concentrations of GI254023X, the proliferation-inhibitive curve was assayed and plotted by CCK-8 method, the cell viability and apoptosis were detected by flow cytometry with Annexin V/7-AAD double staining. The cleavage of Notch1 protein (cleaved notch1) was determined by Western blot. The transcripts of Notch1 target gene Hes-1 were detected by real-time PCR.
RESULTSThe GI254023X inhibited the proliferation of H929 cells in the time- and dose- dependent manners. As compared with the control group, the apoptosis of cells increased along with enhancement of GI254023X concentration; The expression of cleaved Notch1 was down-regulated after the treatment with GI254023X. The levels of Hes-1 mRNA transcripts in H929 cells was reduced in GI254023X treated group.
CONCLUSIONGI254023X can remarkably inhibit the proliferation and induce the apoptosis of H929 cells. Its mechanism may be associated with inbihition of Notch1 activation.