Inhibitory effect of histone deacetylase inhibitor LBH589 on multiple myeloma MM1R cells in vitro.
- Author:
Ling ZHANG
1
;
Yan-Ping MA
;
Gu JIA
;
Yu-Jin LU
;
Li ZHANG
;
Hong LU
;
Ming-Xing CHANG
Author Information
1. Department of Hematology, Shanxi Medical University Second Hospital, Shanxi Province, China.
- Publication Type:Journal Article
- MeSH:
Acetylation;
drug effects;
Apoptosis;
drug effects;
Boronic Acids;
pharmacology;
Bortezomib;
Cell Cycle;
drug effects;
Cell Line, Tumor;
Histone Deacetylase Inhibitors;
pharmacology;
Humans;
Hydroxamic Acids;
pharmacology;
Indoles;
pharmacology;
Multiple Myeloma;
pathology;
Pyrazines;
pharmacology
- From:
Journal of Experimental Hematology
2012;20(5):1122-1126
- CountryChina
- Language:Chinese
-
Abstract:
This study was purposed to explore the effect of a new generation of histone deacetylase inhibitor LBH589 alone or combined with bortezomib (Bor) on multiple myeloma cells (MM1R) in vitro. The effect of LBH589 (10, 20, 50 nmol/L) alone or combined with Bor (10, 20 nmol/L) on MM1R proliferation was detected by MTT method; the effect of LBH589 on cell cycle and apoptosis of MM1R cells were determined by flow cytometry; the histone H4 acetylation level of MM1R cells treated with LBH589 (10, 20, 50 nmol/L) for 24 h was analyzed by Western blot. The results showed that the LBH589 alone or combined with Bor all could inhibit the proliferation of MM1R cells in a concentration- and time-dependent manner. After MM1R cells were treated with drugs for 48 h, the cells in G(0)/G(1) phase increased, the cells in G(2)/M and S phase decreased, suggesting the arrest of cells in G(0)/G(1) phase, at the same time, the apoptosis rate of MM1R cells treated with drugs increased in a concentration-dependent manner, while the effect of LBH589 combined with Bor was more obvious than that of LBH589 alone (P < 0.001). Western blot analysis showed that the histone H4 acetylation level was enhanced in concentration-dependent manner after MM1R cells were treated with different concentrations of LBH589 for 24 h. It is concluded that the LBH589 can inhibit the proliferation of MM1R cells, block the cell cycle, induce cell apoptosis, moreover LBH589 combined with Bor has synergistic effect on MM1R cells.
