本文選題：S-腺苷甲硫氨酸 + VEGF-C��； 參考：《寧夏醫(yī)科大學》2015年碩士論文

【摘要】：目的觀察S-腺苷甲硫氨酸(S-adenosylmethionine,SAM)對血管內(nèi)皮生長因子-C(Vascular Endothelial Growth Factor-C,VEGF-C)基因啟動子序列甲基化狀態(tài)及表達的影響,以及對胃癌細胞MGC803、SGC7901及裸鼠移植瘤生長的影響。探討其抗腫瘤效應及可能機制,尋求胃癌治療的新途徑。方法亞硫酸氫鹽基因組測序法(Bisulfite Genomic DNA Sequencing Analysis,BGS)檢測胃癌細胞中VEGF-C基因啟動子序列在SAM作用前后的甲基化狀態(tài);RT-q PCR和Western blotting分別檢測胃癌細胞中VEGF-C m RNA和蛋白在SAM作用前后的表達水平;MTT法和流式細胞術(shù)分別檢測SAM對胃癌細胞增殖和凋亡的影響;建立裸鼠移植瘤模型檢測SAM在體內(nèi)對腫瘤生長的影響;免疫組織化學法檢測人胃癌裸鼠移植瘤在SAM作用前后VEGF-C的表達。結(jié)果VEGF-C在胃癌細胞MGC803、SGC7901中呈低甲基化狀態(tài),經(jīng)SAM處理后其甲基化程度增高;SAM處理MGC803、SGC7901細胞后,VEGF-C m RNA和蛋白表達明顯降低(P0.05);隨藥物濃度增大,腫瘤細胞增殖受到明顯抑制(P0.05),凋亡率也明顯增加(P0.05);SAM對人胃癌裸鼠移植瘤的生長有明顯的抑制作用,作用前后移植瘤體積有顯著差異(P0.05);SAM抑制了人胃癌裸鼠移植瘤中VEGF-C的表達。結(jié)論SAM可以改變胃癌細胞中VEGF-C啟動子序列的低甲基化狀態(tài),并且抑制其表達,最終抑制胃癌的生長。SAM作為一種潛在的抗腫瘤藥物,表觀遺傳學調(diào)控可能是其抗腫瘤作用的一個新機制。
[Abstract]:Objective to investigate the effects of S-adenosylmethionine (SAM) on the methylation and expression of vascular endothelial growth factor-C (VEGF-C) gene promoter, and on the growth of gastric cancer cell line MGC803SGC7901 and xenografts in nude mice. To explore the anti-tumor effect and possible mechanism of gastric cancer and seek a new approach to the treatment of gastric cancer. Methods Bisulfite Genomic DNA sequencing assay (BGS) was used to detect the methylation status of VEGF-C promoter sequence in gastric cancer cells before and after SAM. RT-PCR and Western blotting were used to detect VEGF-C mRNA and protein in gastric cancer cells before and after SAM. The effect of SAM on proliferation and apoptosis of gastric cancer cells was detected by MTT assay and flow cytometry. The effect of SAM on the growth of human gastric carcinoma xenografts in vivo and the expression of VEGF-C before and after SAM in nude mice were detected by immunohistochemical method. Results VEGF-C was hypomethylated in gastric cancer cell line MGC803hSGC7901. The methylation degree of VEGF-C was increased after SAM treatment. The expression of VEGF-C mRNA and protein in gastric cancer cell line MGC803 + SGC7901 was significantly decreased after SAM treatment (P0.05), and the expression of VEGF-C mRNA and protein decreased with the increase of drug concentration. Tumor cell proliferation was significantly inhibited (P0.05) and apoptosis rate was significantly increased (P0.05). SAM significantly inhibited the growth of human gastric carcinoma xenografts in nude mice (P0.05). (P0.05) SAM inhibited the expression of VEGF-C in human gastric carcinoma xenografts. Conclusion SAM can change the hypomethylation of VEGF-C promoter sequence and inhibit the expression of VEGF-C promoter in gastric cancer cells, and ultimately inhibit the growth of gastric cancer. SAM is a potential antitumor drug. Epigenetic regulation may be a new mechanism of its anti-tumor effect.
【學位授予單位】：寧夏醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2015
【分類號】：R735.2

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相關(guān)期刊論文 前1條

1 段耀星;達明緒;姚繼彬;張永斌;;胃癌組織血管內(nèi)皮生長因子C啟動子甲基化狀態(tài)檢測及意義[J];蘭州大學學報(醫(yī)學版);2014年02期

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本文編號：2104970