本文選題：肝癌　切入點：FASN　出處：《重慶醫(yī)科大學》2017年碩士論文

【摘要】：肝癌是全世界癌癥死亡的最主要原因之一。由于其高度的轉移傾向,活躍的血管生成和快速增殖,復發(fā)和較差的預后成為了肝癌治療及治愈的主要障礙。為了進一步研究FASN腫瘤細胞遷移、侵襲的機制,我們在本研究中,利用免疫組織化學、組織芯片、Transwell和劃痕實驗等實驗技術驗證了以前的研究結果,在肝癌組織樣品中FASN的表達明顯高于非癌組織樣品(癌旁),并影響肝癌細胞遷移、侵襲能力。收集敲除及未敲除FASN乙肝相關性肝癌細胞(HepG2.2.15)的分泌蛋白后,使用同位素標記相對和絕對定量(iTRAQ)技術以及質譜分析的方法分析鑒定差異表達的蛋白(DEPS)。我們一共識別出了30種有意義的DEP,其中8種蛋白明顯上調,22種蛋白明顯下調。經過RT-PCR和Western blotting分析驗證,DEP的結果與iTRAQ一致。抑制FASN可以明顯降低IGFBP1水平,同時我們發(fā)現HIF-1α的表達,活性以及泛素化作用也明顯下降。因此,抑制FASN可通過降低IGFBP1表達和HIF-1α的表達、活性及泛素化作用,抑制肝癌細胞遷移,侵襲和愈合。
[Abstract]:Liver cancer is one of the leading causes of cancer death in the world. Recurrence and poor prognosis have become major obstacles to the treatment and cure of liver cancer. In order to further study the mechanism of migration and invasion of FASN tumor cells, we used immunohistochemistry in this study. Tissue microarray Transwell and scratch test were used to verify the results of previous studies. The expression of FASN in HCC tissues was significantly higher than that in non-cancerous tissues (paracarcinoma) and affected the migration of HCC cells. Invasive ability. The secreted proteins of FASN HepG2.2.15 cells were collected after knockout and non-knockout. Relative and absolute quantitative iTRAQ techniques and mass spectrometry were used to analyze and identify the differentially expressed proteins. We identified a total of 30 significant DEPs, of which 8 proteins significantly up-regulated 22 proteins. The results of RT-PCR and Western blotting analysis were consistent with that of iTRAQ. Inhibition of FASN could significantly reduce IGFBP1 level. At the same time, we found that the expression, activity and ubiquification of HIF-1 偽 also decreased significantly. Therefore, inhibition of FASN can inhibit the migration, invasion and healing of hepatoma cells by reducing the expression of IGFBP1 and the expression, activity and ubiquification of HIF-1 偽.
【學位授予單位】：重慶醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R512.62;R735.7

【參考文獻】

相關期刊論文 前1條

1 Mahmoud Fathy Dondeti;Eman Anwar El-Maadawy;Roba Mohamed Talaat;;Hepatitis-related hepatocellular carcinoma: Insights into cytokine gene polymorphisms[J];World Journal of Gastroenterology;2016年30期

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本文編號：1661927