Bortezomib combined with homoharringtonine or arsenious acid induced apoptosis in HL-60 cells and its mechanism
10.3760/cma.j.issn.1009-9921.2013.09.006
- VernacularTitle:硼替佐米联合三氧化二砷或高三尖杉酯碱体外诱导白血病细胞株HL-60凋亡及其机制
- Author:
Yunbi FU
;
Fanyi MENG
;
Li LI
;
Qixin SUN
- Publication Type:Journal Article
- Keywords:
Cells,HL-60;
Bortezomib;
Homoharringtonine;
Arsenious acid;
Apoptosis
- From:
Journal of Leukemia & Lymphoma
2013;22(9):528-531
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the apoptosis effect induced by bortezomib combined with homoharringtonine or arsenious acid in HL-60 cell line and the mechanism.Methods Cell' s apoptosis was demonstrated by MTT assay and Hoechst33342 staining.Expression of bcl-2,Caspase-9,Caspase-3 and PARP protein was detected by Western blot.Results HL-60 cells' apoptosis could be induced by bortezomib,homoharringtonine and arsenious acid respectively.Proliferation inhibition of HL-60 cells could be enhanced significantly when treated by bortezomib combined with homoharringtonine or arsenious acid compared with treated by any of the three drugs alone (P ＜ 0.05).At the same time morphology shows the apoptosis induced by drugs combined is more obviously than by one drug.Western blot showed bcl-2 protein was down-regulated and Caspase-9,Caspase-3 and PARP proteins were all cleaved activation when cells were treated by 15 μmol/ L arsenious acid alone,but only cleaved activation of PARP and down-regulation of bcl-2 protein be detected when cells were treated with 30 nmol/L homoharringtonine alone,expression of Caspase-9 and Caspase-3 had no change compared with the control.The changes of associated proteins were paralleled with the cell' s apoptosis when treated with combined drugs.Conclusion HL-60 cells' apoptosis effect is inhanced significantly when bortezomib combined with homoharringtonine or arsenious acid.Arsenious acid and bortezomib can inhibit caspase signaling pathway and down-regulate the expression of bcl-2 protein together,but homoharringtonine and bortezomib can only down-regulate the expression of bcl-2 protein and induce cleaved activation of PARP together.
