Effects Of EZH2 Inhibitor DZNep On The Proliferation,Apoptosis And Cell Cycle Of NK/T Cell Lymphoma Cells

Background NK/T cell lymphoma is a special type of non-Hodgkin's lymphoma(NHL)characterized by destruction of nose and facial midline and has obvious regional and racial susceptibility,which is more common in Asia and South America.In addition,it is characterized by high invasiveness,poor prognosis,high recurrence rate,insidious onset and easy missed diagnosis.In terms of treatment,there is still a lack of unified treatment plan.Enhancer of zeste homolog 2(EZH2),a core subunit of polycomb repressive complex 2(PRC2),has the activity of histone methylase and can catalyze trimethylation of histone H3 lysine27(H3K27me3),which regulates gene expression at the epigenetic level.It has been found that EZH2 expression is abnormal in various tumors such as prostate cancer and breast cancer,and is closely related to the occurrence,development,prognosis and drug resistance of tumors.In NK/T cell lymphomas,EZH2 is also highly expressed,and it does not play a carcinogenic role through the classical H3K27me3 pathway,but directly activates the expression of cyclin D1(CCND1)by binding to the promoter of CCND1 as a transcriptional activator,leading to abnormal proliferation of tumor cells.3-Deazaneplanocin(DZNep)was the first selected inhibitor of EZH2.As a targeted inhibitor of EZH2,DZNep can not only inhibit the histone methylase activity of EZH2,but also degrade EZH2 protein.Currently,targeted therapy for EZH2 has not been reported in the studies on NK/T cell lymphoma.The objective of this study is to explore the effects of EZH2 inhibitor DZNep on the proliferation,apoptosis and cell cycle of NK/T cell lymphoma cell line SNK-6.Methods After treated with DZNep,the proliferation of SNK-6 cells was measured by CCK-8 assay.The cell cycle was evaluated by flow cytometry.The apoptosis was determined by Annexin V/PI double staining.The amounts of EZH2,Cleaved Caspase-3 and Cleaved PARP protein were detected by Western blot.Results After treated with DZNep,the level of EZH2 was down-regulated when compared with control cells.The proliferation of SNK-6 cells was inhibited in a dose and time dependent manner and the cells were stagnated in G1/S phase.The apoptosis was induced and the expressions of Cleaved Caspase-3 and Cleaved PARP were up-regulated.