Effect of 5-aza-2'-deoxycytidine combined with trichostatin A on RPMI-8226 cell proliferation, apoptosis and DLC-1 gene expression.
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.
Department of Hematology, The Affiliated Hospital of Medical College, Qingdao University, Qingdao 266000, Shandong Province, China.
Jing
J
Guo
Department of Hematology, The Affiliated Hospital of Medical College, Qingdao University, Qingdao 266000, Shandong Province, China.
Xian-Qi
XQ
Feng
Department of Neurology, The Affiliated Hospital of Medical College, Qingdao University, Qingdao 266000, Shandong Province, China.
Shu-Min
SM
Nie
Department of Hematology, The Affiliated Hospital of Medical College, Qingdao University, Qingdao 266000, Shandong Province, China.
Zhan
Z
Su
Department of Hematology, The Affiliated Hospital of Medical College, Qingdao University, Qingdao 266000, Shandong Province, China.
Xue
X
Shi
Department of Hematology, The Affiliated Hospital of Medical College, Qingdao University, Qingdao 266000, Shandong Province, China.
Zhong-Guang
ZG
Cui
Department of Hematology, The Affiliated Hospital of Medical College, Qingdao University, Qingdao 266000, Shandong Province, China.
Ling
L
Zhang
Gout Laboratory, The Affiliated Hospital of Medical College, Qingdao University, Qingdao 266000, Shandong Province, China.
Shi-Guo
SG
Liu
Department of Hematology, The Affiliated Hospital of Medical College, Qingdao University, Qingdao 266000, Shandong Province, China.
Fan-Jun
FJ
Meng
Department of Hematology, The Affiliated Hospital of Medical College, Qingdao University, Qingdao 266000, Shandong Province, China.
Chun-Ting
CT
Zhao
D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001374:Azacitidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D000077209:Decitabine; D020690:GTPase-Activating Proteins / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D006877:Hydroxamic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D009101:Multiple Myeloma / Q000235:genetics / Q000473:pathology*; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
D000964:Antimetabolites, Antineoplastic; C112352:DLC1 protein, human; D020690:GTPase-Activating Proteins; D006877:Hydroxamic Acids; D025521:Tumor Suppressor Proteins; C012589:trichostatin A; D000077209:Decitabine; D001374:Azacitidine