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Effects of Proteasome Inhibitor Bortezomib Alone and Combination with Daunomycin on Apoptosis and Survivin mRNA Expression of HL-60 Cells

Author: ZhaoShuWen
Tutor: MaLiangMing
School: Shanxi Medical
Course: Department of Hematology
Keywords: Proteasome inhibitor Bortezomib Daunorubicin HL-60 cells Apoptosis Survivin
CLC: R733.7
Type: Master's thesis
Year: 2008
Downloads: 39
Quote: 0
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Abstract


Objective To study the different concentrations of proteasome inhibitor bortezomib (bortezomib, Bor) alone and combined daunorubicin (DNR) on HL-60 cell apoptosis induced by the aim to explore its possible mechanism of apoptosis , and Survivin mRNA expression. Methods Different concentrations of Bor, DNR and the two -drug combination group and control group acting on the HL-60 cells , using the MTT ( tetrazolium salt ) Determination of cells in the 24 hours , 48 hours , 72 hours proliferative activity , and select the strongest effect on cell time period cell apoptosis was detected by flow cytometry , RT-PCR detection of expression of Survivin mRNA . Results 1.MTT Results : 5nmol/lBor effect 24 hours of HL-60 cell proliferation and induce apoptosis . With the increase in the concentration and treatment time increased cell apoptosis rate increased significantly , 10nmol/lBor combined effects of 72 hours with 1.0umol/lDNR highest rate of apoptosis , with the same dose of the two drugs alone there were significant differences ( P <0.01). (2) Flow cytometry showed that the concentrations after 72 hours incubation cells were seen , compared with the control group had significant statistical significance (P <0.01), with 10nmol/lBor combined with 1.0umol/lDNR role in apoptosis highest rate of 45.84% , compared with the same dose of the two drugs alone had significant differences (P <0.01). 3.RT-PCR analysis showed that : with the increase of drug concentration , Survivin mRNA expression decreased gradually, and the two drugs alone and there was an interaction between the combined group to 10nmol/lBor combined effects of 72 hours with 1.0umol/lDNR Survivin mRNA expression lowest . Conclusion Bor could significantly inhibit the proliferation of HL-60 cells and induce apoptosis , Bor joint DNR in HL-60 cells in a synergistic effect , and significantly reduced the expression of Survivin gene , which may induce HL-60 cell apoptosis world.

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CLC: > Medicine, health > Oncology > Hematopoietic and lymphoid neoplasms > Leukemia
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