Study On The Inhibitory Effect Of Chidamide On HDAC-STAT3 Pathway In Diffuse Large B-cell Lymphoma

Objective:To investigate the effects of the deacetylase inhibitor Chidamide on proliferation,apoptosis and related STAT3 pathway mechanism of diffuse large B-cell lymphoma SU-DHL2,OCI-LY3 and MZ cells.Methods:1.CCK8 method was used to verify the effect of Chidamide on the viability of diffuse large B-cell lymphoma SU-DHL2,OCI-LY3 and MZ cells.2.Flow cytometry was used to study the effects of Chidamide on the apoptosis of diffuse large B-cell lymphoma SU-DHL2,OCI-LY3 and MZ cells.The protein expression of Cleaved caspase3 and Bcl-2 was detected by Western blot.3.Co-immunoprecipitation method was used to detect the interaction between type I HDAC protein and STAT3 protein in diffuse large B-cell lymphoma SU-DHL2,OCI-LY3and MZ cells.4.Western blot was used to detect the effects of Chidamide on HDAC-STAT3pathway-related proteins at preset concentrations,and to study its mechanism of action.Results:1.CCK8 results showed that the IC₅₀0 of Chidamide on diffuse large B-cell lymphoma SU-DHL2,OCI-LY3 and MZ cells after 72h was 2.722μmol/L,1.353μmol/L,4.183μmol/L respectively.2.Chidamide promotes the apoptosis of diffuse large B-cell lymphoma SU-DHL2,OCI-LY3 and MZ cells,which increases the expression of the pro-apoptotic protein Cleaved caspase3 and decreases the expression of the anti-apoptotic protein Bcl-2.3.There is an interaction between type I HDAC protein and STAT3 protein in diffuse large B-cell lymphoma SU-DHL2,OCI-LY3 and MZ cells.4.Chidamide can inhibit the expression of type I HDAC protein,total STAT3 protein and its phosphorylated P-STAT3（Y705）,P-STAT3（S727）and AcSTAT3（K685）proteins are inhibited,type I HDAC and STAT3 proteins expression are positively correlated.Conclusion:1.Chidamide has a strong inhibitory activity on diffuse large B-cell lymphoma SU-DHL2,OCI-LY3 and MZ cells,and has a significant concentration and time dependence.2.Type I HDAC protein interacts with STAT3 protein in diffuse large B-cell lymphomas SU-DHL2,OCI-LY3 and MZ cells.Type I HDAC acts as a target for Chidamide.Chidamide can inhibit both type I HDAC and STAT3 proteins,which in turn affects the STAT3 signaling pathway.By inhibiting STAT3 activation,low phosphorylation and low acetylation levels work together to inhibit the transcriptional activity of STAT3,which in turn stimulates the caspase3 apoptosis pathway to induce apoptosis and inhibits tumor cell activity and proliferation.