Inhibitory Effect And Mechanism Of HDAC Inhibitor HS270 In NK/T Cell Lymphoma

Objective:This study aimed to investigate the inhibitory effect and related mechanism of a novel histone deacetylase inhibitor HS270 in NK/T cell lymphoma,and to provide a certain experimental basis for exploring new therapeutic directions for NK/T cell lymphoma.Methods:1.The effects of HS270,SAHA and Chi on the proliferation of NKTCL cell lines were detected by CCK8 proliferation inhibition assay.2.The difference of HS270,SAHA and Chi on apoptosis and cycle of NKTCL cell lines were detected by flow cytometry.3.The antitumor mechanism of HS270 on NKTCLwas investigated by RNA-seq.4.RT-q PCR and western blotting were used to detect the m RNA and the protein expression levels of P53,CDK2 and CDK4 in NKTCL cell lines treated by HS270,respectively.5.NKTCL model in nude mice was established,and the tumor suppressive effect of HS270 was observed in vivo.Results:1.HS270 had a strong inhibitory effect on the proliferation of NK/T cell lymphoma,and it was better than the isotype drugs SAHA and Chi(P<0.05),in a time-dose-dependent manner.2.HS270 can promote the apoptosis of NKTCL cell lines,and its pro-apoptotic effect was better than Chi(P<0.05),and similar to SAHA(P>0.05).3.HS270 can arrest the cell cycle of NKTCL lymphoma cell lines in G0/G1 phase,and the cycle arrest effect was better than Chi(P<0.05),and similar to SAHA(P>0.05).4.RNA-Seq results suggested that HS270 mainly acts on cell cycle-related pathways in NKTCL cells.5.RT-qPCR detection results showed that the m RNA expression levels of P53,CDK2,and CDK4 in NKTCL cells treated with HS270 were down-regulated compared with the control group(P<0.05);Western blotting results showed that the protein expression levels of P53,CDK2,and CDK4 were compared with the control group The expression was down-regulated,and the P21 protein level was up-regulated(P<0.05).Conclusion:1.The histone deacetylase inhibitor HS270 can inhibit the proliferation of NK/T cell lymphoma cell lines,arrest the cell cycle and induce apoptosis,it also can effectively inhibit the tumor growth of the NKTCL mouse xenograft model.2.HS270 may induce G0/G1 phase arrest by affecting the P21/CDK2/CDK4-related pathways of NKTCL cell lines,and it also can induce NKTCL cell apoptosis to play a tumor suppressive role.