Effect of 5-aza-2'-deoxycytidine combined with trichostatin A on RPMI-8226 cell proliferation, apoptosis and DLC-1 gene expression.
10.7534/j.issn.1009-2137.2014.02.017
- Author:
Jing GUO
1
;
Xian-Qi FENG
1
;
Shu-Min NIE
2
;
Zhan SU
1
;
Xue SHI
1
;
Zhong-Guang CUI
1
;
Ling ZHANG
1
;
Shi-Guo LIU
3
;
Fan-Jun MENG
1
;
Chun-Ting ZHAO
1
Author Information
1. Department of Hematology, The Affiliated Hospital of Medical College, Qingdao University, Qingdao 266000, Shandong Province, China.
2. Department of Neurology, The Affiliated Hospital of Medical College, Qingdao University, Qingdao 266000, Shandong Province, China.
3. Gout Laboratory, The Affiliated Hospital of Medical College, Qingdao University, Qingdao 266000, Shandong Province, China.
- Publication Type:Journal Article
- MeSH:
Antimetabolites, Antineoplastic;
pharmacology;
Apoptosis;
drug effects;
Azacitidine;
administration & dosage;
analogs & derivatives;
pharmacology;
Cell Line, Tumor;
Cell Proliferation;
drug effects;
GTPase-Activating Proteins;
metabolism;
Gene Expression;
drug effects;
Humans;
Hydroxamic Acids;
administration & dosage;
pharmacology;
Multiple Myeloma;
genetics;
pathology;
Tumor Suppressor Proteins;
metabolism
- From:
Journal of Experimental Hematology
2014;22(2):357-363
- CountryChina
- Language:English
-
Abstract:
This study was aimed to investigate the effects of the DNA methylation inhibitor 5-aza-2'-deoxycytidine (5-Aza-CdR) and histone deacetylase inhibitor trichostatin A (TSA) on DLC-1 gene transcription regulation and molecular biological behaviours in the human multiple myeloma RPMI-8226 cells. The cells were treated respectively with 5-Aza-CdR and TSA alone, or the both combination; the cell proliferation and apoptosis, DLC-1 expression, the protein expression of Ras homolog family member A (RhoA) and Ras-related C3 botulinum toxin substrate 1 (Rac1) were examined by CCK-8 method, RT-PCR and ELISA, respectively. The results showed that the 5-Aza-CdR and TSA had cell growth inhibitory and apoptosis-inducing effects in dose-dependent manner (P < 0.05). Compared with a single drug (5-Aza-CdR or TSA alone), the effects were significantly enhanced after treatment with the combination of 5-Aza-CdR and TSA (P < 0.05). DLC-1 was weakly expressed in the control group; the treatment with 5-Aza-CdR alone enhanced its re-expression dose-dependently (P < 0.05). Compared with 5-Aza-CdR alone, 5-Aza-CdR plus TSA enhanced DLC-1 re-expression significantly.Compared with the control, 5-Aza-CdR and TSA significantly decreased RhoA and Rac1 protein expression (P < 0.05). It is concluded that 5-Aza-CdR and TSA can effectively reverse DLC-1 expression of RPMI-8226 cells; TSA has a synergistic effect on its re-expression. 5-Aza-CdR and TSA have significant cell growth inhibitory and apoptosis-inducing effects on RPMI-8226 cells. These effects may be related to the inhibition of Rho/Rho kinase signalling pathway.
