本文選題：G9a + 腦膠質(zhì)瘤　； 參考：《福建醫(yī)科大學(xué)》2014年碩士論文

【摘要】：【目的】：研究組蛋白甲基化酶G9a、組蛋白H3K9me2、組蛋白H3K9me1在人類腦膠質(zhì)瘤組織和癌旁組織中表達(dá)的差異及臨床意義。觀察甲基化酶G9a抑制劑BIX-01294在體外人類腦膠質(zhì)瘤U251細(xì)胞株增殖、凋亡的改變、組蛋白H3K9、H3K27甲基化及組蛋白H3乙酰化水平的影響，初步探討其機制。 【方法】：1、免疫組織化學(xué)方法檢測人類腦膠質(zhì)瘤組織和癌旁組織中組蛋白甲基化酶G9a、組蛋白H3K9me2、組蛋白H3K9me1蛋白的表達(dá)差異，統(tǒng)計學(xué)分析探討其臨床意義。2、 MTS法繪制BIX-01294作用人類腦膠質(zhì)瘤U251細(xì)胞后的生長曲線，TUNEL法檢測U251細(xì)胞調(diào)亡率的變化。3、Western blot法檢測GX-01294作用人類腦膠質(zhì)瘤U251細(xì)胞后凋亡相關(guān)蛋白BCL-2、Bax、Caspase-9、Caspase-3；組蛋白H3K9me、H3K9me2、H3K9me3、組蛋白H3K27me1、組蛋白H3K27me2、組蛋白H3乙�；癄顟B(tài)的影響。 【結(jié)果】：1、在腦膠質(zhì)瘤的癌組織中組蛋白甲基轉(zhuǎn)移酶G9a蛋白的陽性率為86%（43/50），癌旁組織中陽性率為42%（21/50），，p0.01，有統(tǒng)計學(xué)意義；癌組織中組蛋白H3K9me2的陽性率為82%（41/50），癌旁組織中陽性率為38%（19/50），確切概率法檢驗，χ2=18.38，p0.01；組蛋白甲基轉(zhuǎn)移酶G9a蛋白和組蛋白H3K9me2的表達(dá)與腦膠質(zhì)瘤WHO分級相關(guān)；腦膠質(zhì)瘤的癌組織中組蛋白H3K9me的陽性率為54%（27/50），癌旁組織中陽性率為44%（22/50），確切概率法檢驗，χ2=1.21，p＞0.05，無統(tǒng)計學(xué)意義。2、BIX-01294抑制人類腦膠質(zhì)瘤U251細(xì)胞增殖；下調(diào)BCL-2，上調(diào)Bax、 caspase-3、caspase-9，誘導(dǎo)細(xì)胞凋亡。3、 BIX-01294下調(diào)組蛋白H3K9me1、H3K9me2及組蛋白H3K27me1、組蛋白H3K27me2水平，而對組蛋白H3K9me3及組蛋白H3乙�；療o影響。 【結(jié)論】：1、腦膠質(zhì)瘤癌組織中組蛋白甲基化酶G9a、H3K9me2高表達(dá)，與腦膠質(zhì)瘤WHO分級相關(guān)，提示G9a、H3K9me2可能有促進(jìn)膠質(zhì)瘤的發(fā)生、發(fā)展作用。2、BIX-01294可以抑制腦膠質(zhì)瘤細(xì)胞增殖，啟動凋亡程序、誘導(dǎo)腫瘤細(xì)胞凋亡，進(jìn)一步研究發(fā)現(xiàn)組蛋白H3K9、H3K27甲基化改變導(dǎo)致染色體構(gòu)象改變可能是其機制， BIX-01294可能成為治療腦膠質(zhì)瘤的潛在新藥。
[Abstract]:[objective]: to study the difference of expression of protein methylase G9a, histone H3K9me2 and histone H3K9me1 in human glioma and paracancerous tissues and its clinical significance. To observe the effect of methylase G9a inhibitor BIX-01294 on the proliferation and apoptosis of human glioma cell line U251 in vitro, the effect of histone H3K9, H3K27 methylation and histone H3 acetylation, and to explore its mechanism. [methods] the expression of histone methylase G9a, histone H3K9me2 and histone H3K9me1 protein in human glioma and paracancerous tissues were detected by immunohistochemistry. The clinical significance of U251 cells was studied by statistical analysis. The growth curve of U251 cells induced by BIX-01294 was plotted by MTS method. Tunel method was used to detect the apoptosis rate of U251 cells after U251 cells were treated with GX-01294. The apoptosis related to U251 cells induced by GX-01294 was detected by Western blot. The effects of histone H3K9me2, histone H3K27me1, histone H3K27me2, histone H3 acetylation state. [results] the positive rate of histone methyltransferase G9a protein in glioma tissues was 8643 / 50, and the positive rate in adjacent tissues was 42%. The positive rate of histone H3K9me2 in cancer tissues was 82 / 41 / 50 and 38 / 38 / 50 in adjacent tissues. The positive rate of histone H3K9me2 and histone H3K9me2 were correlated with the WHO grade of gliomas by 蠂 2 + 18.38% p0.01.The expression of histone methyltransferase G9a and histone H3K9me2 were correlated with the WHO grade of gliomas. The positive rate of histone H3K9me in glioma tissues was 54 / 27 / 50 and that in adjacent tissues was 44 / 22 / 50. The exact probability test showed that 蠂 2 + 1. 21% p > 0. 05. There was no statistical significance. 2BIX-01294 inhibited the proliferation of human glioma U251 cells. Down-regulation of BCL-2, up-regulation of Bax, caspase-3 and caspase-9, induction of apoptosis. BIX-01294 down-regulated the levels of histone H3K9me2 and histone H3K27me1, histone H3K27me2, but had no effect on histone H3K9me3 and histone H3 acetylation. [conclusion] the high expression of histone methylase G9aOH3K9me2 in glioma tissues is related to the WHO grading of gliomas, suggesting that G9aH3K9me2 may promote the development of glioma, and the developmental action of .2BIX-01294 can inhibit the proliferation of glioma cells and initiate the process of apoptosis. Apoptosis of tumor cells was induced by histone H3K9 and H3K27 methylation, which may be the mechanism of chromosome conformation change. BIX-01294 may be a potential new drug in the treatment of glioma.
【學(xué)位授予單位】：福建醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R739.4

【參考文獻(xiàn)】

相關(guān)期刊論文 前1條

1 ;Expression of histone methyltransferase G9a and clinical significance in extrahepatic cholangiocarcinoma[J];Chinese-German Journal of Clinical Oncology;2008年01期

本文編號：1865344