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  本文選題：組蛋白去乙�；敢种苿� + T細胞淋巴瘤��； 參考：《山西醫(yī)科大學》2017年碩士論文

【摘要】：目的:研究新型組蛋白去乙�；敢种苿〧a的抗腫瘤活性作用及其抑制人T細胞淋巴瘤細胞的增殖機制。方法:1、通過CCK-8法檢測不同濃度Fa(1.56,3.125,6.25,12.5,25,50μM)對Jurkat細胞作用24、48、72h的增殖抑制作用,并計算出三個時間段細胞增殖抑制半數(shù)的藥物濃度(IC50);2、流式細胞術觀察不同濃度Fa對Jurkat細胞作用72h后誘導細胞周期阻滯的作用以及25μM Fa作用細胞24、48、72h后細胞周期變化;3、Western blot測定Fa對Jurkat細胞中cyclin D、CDK4、p21~(cip/WAF)的蛋白表達影響;4、RT-PCR測定Fa對Jurkat細胞中HDAC1、HDAC2、HDAC3基因的表達影響;5、實驗數(shù)據(jù)以均數(shù)±標準差表示,應用Prism 5軟件進行統(tǒng)計分析,采用單因素方差分析(One-way ANOVA)及兩樣本均數(shù)比較的t檢驗,P0.05表示差異具有統(tǒng)計學意義。結果:CCK-8檢測結果顯示,以正常細胞作對照,不同濃度Fa作用Jurkat細胞24、48、72h后,細胞增殖抑制半數(shù)的藥物濃度(IC50)分別是88.72±0.13、25.45±0.03、12.21±0.07μM,作用72h時,細胞生長活力百分比由95.6±2.57%減少至11.4±1.41%,并且呈濃度和時間依賴性;流式細胞術分析結果顯示不同濃度Fa作用Jurkat細胞72h后可以產生G0/G1期細胞周期阻滯,并且呈濃度依賴性。25μM Fa作用時,隨著時間延長,處于G0/G1期細胞百分比由42.54±2.11%增加至61.42±0.59%;p21~(cip/WAF)蛋白表達水平有所上升,cyclin D、CDK4蛋白表達下調;Fa藥物能夠有效抑制HDAC1、HDAC2、HDAC3的活性。結論:Fa對T細胞淋巴瘤細胞株具有一定的抗腫瘤活性,其機制與誘導細胞凋亡周期阻滯及上調抑癌基因p21~(cip/WAF)表達有關。
[Abstract]:Aim: to study the antitumor activity of a novel histone deacetylase inhibitor Fa and its mechanism of inhibiting the proliferation of human T cell lymphoma cells. Methods CCK-8 assay was used to detect the proliferation inhibitory effect of different concentrations of Fa 1.56C 3.125C 6.255C 2550 渭 M on Jurkat cells for 72 h. The cell cycle arrest induced by different concentration of Fa for 72 h and the cell cycle change after treatment with 25 渭 M Fa for 72 h were observed by flow cytometry. Effect of Fa on the protein expression of cyclin DCDK4p21cip-pWAF in Jurkat cells by Western blot the effect of Fa on the expression of HDAC1HDAC2HDAC3 gene in Jurkat cells was determined by RT-PCR. The experimental data were expressed as mean 鹵standard deviation. The statistical analysis was carried out by using Prism 5 software. One-way ANOVA) and the t test of the mean of the two samples were used to show the difference was statistically significant. Results the cell proliferation inhibition 50 (IC50) was 88.72 鹵0.1325.45 鹵0.03C 12.21 鹵0.07 渭 M at 72 h after treatment with Fa at different concentrations of Fa. Results the results showed that the IC50 concentration was 88.72 鹵0.1325.45 鹵0.03n 12.21 鹵0.07 渭 M, respectively, in Jurkat cells treated with different concentrations of Fa for 72 h, the results showed that the concentration of IC50 was 88.72 鹵0.135.45 鹵0.03U 12.21 鹵0.07 渭 M. The percentage of cell growth activity decreased from 95.6 鹵2.57% to 11.4 鹵1.41%, and showed a concentration-and time-dependent manner. Flow cytometry showed that different concentrations of Fa could induce cell cycle arrest in G0/G1 phase after 72 h of treatment with Fa in a concentration-dependent manner. As time went on, the percentage of cells in G0/G1 phase increased from 42.54 鹵2.11% to 61.42 鹵0.59%. ConclusionTwo Fa has antitumor activity on T cell lymphoma cell lines, and its mechanism is related to the arrest of apoptosis cycle and the up-regulation of the expression of tumor suppressor gene p21cip/ WAF.
【學位授予單位】：山西醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R733.1

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