Effect Of Bortezomib On Proliferation And Apoptosis Of Human Lymphoma Raji Cells

Non-Hodgkin's lymphoma(NHL) is one of malignant tumors sourced from lymph nodes and(or) extra-nodal lymphoid tissue,NHL patients usually showed good response on traditional chemotherapy(such as COP,CHOP,etc.),but most of them often easily recurred after relief for a few months even several years.The patients could achieve long-term relief time after stronger chemotherapy,but the stronger chemotherapy drugs followed more toxicity and higher mortality rate, which made targeted-therapy for the NHL become a hot spot in recent years.The proteasome inhibitor bortezomib has shown obvious anti-tumor effect on a variety of malignant tumors such as multiple myeloma,colon cancer,chronic lymphocytic leukemia and pancreatic cancer both in vitro and in animal experiments,and it has obvious anti-lymphoma effect.The mechanism are related to prevent tumor growth,angiogenesis and disseminate through specifically inhibiting the ubiquitin - proteasome pathway(UPP),It has tolerable side effect and no cross-resistant drug with other chemodrugs.And foreign studies suggest that bortezomib single or combined other drugs can inhibit proliferation of variety lymphoma cells in vitro.To provide theoretical proof for new curative chemotherapy drugs and combination chemotherapy programs in clinic,we treated human lymphoma cells Raji with bortezomib,and observed the changes of the cells proliferation and cells apoptosis rate.Wright-Giemsa dyeing assay was used to observe apoptosis morphology of lymphoma cells.Detecting proliferation of the cells with bortezomib by the method of MTT.Flow cytometry(FCM) was used to detect apoptosis of lymphoma.The semi-quantitive RT-PCR was used to detect NF-κB and caspase-3 expression in Raji cells.The results showed that evident change of apoptosis morphology was found in Raji cells after treatment with bortezomib for 24 hours,bortezomib can increase the inhibition rates more obviously(P＜0.05),and the inhibition rate was related to the concentration and acting time of bortezomib(P＜0.05).Compared with the control group,bortezomib can increase the apoptosis rates of lymphoma cells,and there is obviously difference(P＜0.05) The semi-quantitive RT-PCR showed that The expression of NF-κB mRNA was decreased after bortezomib treatment of different doses,they were obviously less than the control(P＜0.05),and the expression of NF-κB mRNA was related to the concentration of bortezomib,while The expression of caspase-3 mRNA was upregulated.In conclusion,bortezomib can inhibit Raji cells proliferation,induce cells apoptosis and downregulate the expression of NF-κB and upregulate the expression of caspase-3 in vitro.NF-κB and caspase-3 gene might participate in the Bortezomib induced apoptosis of Raji cells.