Study Of Combined Effect And Mechanism Of Decitabine And Chidamide In Peripheral T Cell Lymphoma Cell Lines

Objective: Peripheral T cell lymphoma(PTCL)is a lymphoma with a high heterogeneity and poor outcomes.Epigenetic changes are involved in the development of this lymphoma.To investigate the effect of epigenetic drugs treating in PTCL,providing a drug combination therapy,we investigate the impact of decitabine and chidamide in proliferation,apoptosis and cell cycle in Hut-78 and Myla-2059 cell lines.Methods: The cell counting kit-8(CCK-8)method was used to measure the effect of singer drug and combination on the proliferation inhibition of Hut-78 and Myla-2059 cell lines.The software Compu Syn was used to calculate the combination index(CI)of drugs and to determine the appropriate concentration of two drugs when combined together.Cell apoptosis was evaluated by Annexin ?/PI staning and analyzed by flow cytometry.The PI staing and flow cytometry were used to detect the cell cycle.The expression of key factors on the JAK2/STAT3 pathway was detected by real-time quantitative polymerase chain reaction(q RT-PCR)and Western Blot method.The data were analyzed by SPSS software(version 21.0)and Graph Pad Prism(version 6.0).Significant differences between samples were analyzed by one-way ANOVA,and comparisons between groups were analyzed by LSD method.A P<0.05 was considered significant.Results: Decitabine and chidamide could produce inhibition of cell proliferation in time-and concentration-dependent manners.The CI suggested that these two drugs had synergistic effects.Chidamide could induce cycle arrest at the G0/G1 phase,but decitatine had no significant effects on cell cycle.The inhibition of the JAK2/STAT pathway by two drugs was not evident on m RNA level.However,on the protein level,the expression of the key genes in JAK2/STAT3 pathway,including p-JAK2,STAT3,p-STAT3,was decreased as well as the anti-apoptotic proteins Mcl-1 and Bcl-XL downstream.Conclusions: Decitabine and Chidamide could induce apoptosis of PTCL cells through the synergistic inhibition of the JAK2/STAT3 pathway.This study provided rationale for clinical application ofhistone deacetylase inhibitors and hypomethylating agents in PTCL.