Influence Of Down-regulation Of Syk By SiRNA On The Proliferation And Apoptosis Of Peripheral T-cell Lymphoma Cells

Background Peripheral T cell lymphoma is a group of malignant tumors with high heterogeneity,clinical manifestation and biological behavior,accounts for about 15% of non Hodgkin lymphoma,The incidence of peripheral T cell lymphoma in Asian population was higher than that in western countries.The disease has a major treatment problem and a low long-term survival because of the minimal effectiveness of conventional CHOP chemotherapy.A novel therapy for peripheral T cell lymphoma is urgently needed.Currently,the results showed that Syk gene was overexpressed in B cell lymphoma.Syk oral inhibitors have been developed,and has been put into clinical application.Therefore,whether the overexpression of Syk is related to the occurrence and development of peripheral T cell lymphoma,and whether it can become a new target of treatment has become a hot topic.The results of our previous study showed that the expression of Syk gene was absent in normal peripheral T lymphocytes,but overexpressed in peripheral T cell lymphoma.The immunohistochemical data showed that the expression of Syk protein was positive in most peripheral T-cell lymphomas tissues,which was consistent with the domestic and foreign research.In this research,we continue to study the role of Syk gene in peripheral T cell lymphoma,and to reveal the effect of Syk gene on peripheral T cell lymphoma cells.Object To investigate the influence of down-regulation of Syk via siRNA on theproliferation and apoptosis of human peripheral T-cell lymphoma HUT-78 cells.Methods1)3 siRNAs targeting Syk were designed,synthetized,and transfected into HUT-78 cells via electroporation.Cells transfected with negative control siRNA and untreated cells were used as controls.2)48 h after transfection,the expression of Syk m RNA and protein were examined by RT-PCR and Western blot respectively,and the most effective Syk siRNA was screened out.3)After 24 h,48 h and 72 h interference,the proliferation of cells and colony formation ability were examined by MTT and soft agar assay.Flow cytometry was used to detect the cell apoptosis.Results1)3 siRNAs notably down-regulated Syk expression at m RNA and protein levels,and the inhibitory effect of siRNA-1 was the most obvious.2)The colony formation of Syk siRNA-1 group was significantly decreased compared with control groups after down-regulation of Syk expression(P<0.05).3)The results of MTT test showed that the proliferation ability of Syk siRNA-1group was significantly decreased compared with control groups(P<0.05).4)Flow cytometry results showed that the apoptosis ratio of Syk siRNA-1 group was about 37%,obviously higher than control groups(P<0.05).Conclusion The down-regulation of Syk expression suppressed the cell proliferation and colony formation ability,and promoted the cell apoptosis of peripheral T-cell lymphomacells.The results showed that Syk gene may play a very important role in the occurrence and development of peripheral T-cell lymphoma,and it may be a novel target for gene therapy of peripheral T-cell lymphoma.