Effect Of5-Aza-2’-Deoxycytidine Combined With Trichostatin A On RPMI-8226Cell Proliferation, Apoptosis, And DLC-1Gene Expression

Objective This study was aimed to investigate the effects of the DNA methylation inhibitor5-aza-2’-deoxycytidine (5-Aza-CdR) and histone deacetylase inhibitor trichostatin A (TSA) on DLC-1gene transcription regulation and molecular biological behaviours in the human multiple myeloma RPMI-8226cells.Methods The cells were treated respectively with one of5-Aza-CdR and TSA, or the combination of both; the cell proliferation and apoptosis, DLC-1expression, the protein expression of Ras homolog family member A (RhoA) and Ras-related C3botulinum toxin substrate1(Rac1) were examined. As a result.Results5-Aza-CdR and TSA statistically significantly showed the dose-dependent cell growth inhibitory and apoptosis-inducing effects(P<0.05). Compared with a single drug (5-Aza-CdR or TSA alone), the effects were significantly stronger after the treatment with the combination of5-Aza-CdR and TSA (P<0.05). DLC-1was weakly expressed in the control group; the treatment with5-Aza-CdR alone enhanced its re-expression dose-dependently (P<0.05). TSA did not; compared with5-Aza-CdR alone,5-Aza-CdR plus TSA enhanced DLC-1re-expression significantly.Compared with the control,5-Aza-CdR and TSA significantly decreased RhoA and Racl protein expression (P<0.05).Conclusion It was concluded that5-Aza-CdR can effectively reverse RPMI-8226cell DLC-1expression; 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-8226cells. These effects may be related to the inhibition of Rho/Rho kinase signalling pathway.