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论文摘要

S-腺苷蛋胺酸对VEGF-C表达及胃癌生长的影响

S-Adenosylmethionine Inhibits Expression of Vascular Endothelial Growth Factor-C Protein and Cellular Proliferation in Gastric Cancer

作者:张永斌, 达明绪, 姚继彬等

Author:ZHANG Yong-bin, DA Ming-xu, YAO Ji-bin. et al

收稿日期:          年卷(期)页码:2015,46(3):384-388

期刊名称:四川大学学报(医学版)

Journal Name:JOURNAL OF SICHUAN UNIVERSITY (MEDICAL SCIENCE EDITION)

关键字:S-腺苷蛋胺酸 血管内皮生长因子-C 甲基化 胃癌

Key words:S-adenosylmethionine VEGF-C Methylation Gastric cancer

基金项目:

中文摘要

目的 通过观察S-腺苷蛋胺酸(SAM)对胃癌细胞(MGC803、SGC7901细胞株)、裸鼠移植瘤生长的影响,以及对胃癌细胞株血管内皮生长因子-C(VEGF-C)表达及甲基化状态的影响,探讨其抗肿瘤效应及可能机制。方法 体外采用MTT法检测不同浓度SAM(终浓度0.5、1、2、4、8、16 mmol/L)对胃癌细胞增殖的影响;亚硫酸氢盐基因组测序法(BGS)检测SAM对胃癌细胞株VEGF-C基因启动子序列甲基化状态的影响;Western blot检测SAM(2、4 mmol/L)对胃癌细胞VEGF-C蛋白表达的影响。体内建立人胃癌裸鼠移植瘤模型,实验组给予SAM〔192 μmol/(kg·d)、768 μmol/(kg·d)〕腹腔注射,对照组给予等量生理盐水腹腔注射, 1次/d, 15 d后检测肿瘤体积变化。结果 SAM处理MGC803、SGC7901细胞后,随药物浓度增大,细胞增殖受到明显抑制(PVEGF-C基因在MGC803、SGC7901细胞中呈高度去甲基化状态,经SAM处理后其甲基化程度增高,VEGF-C蛋白表达降低。SAM对人胃癌裸鼠移植瘤的生长有明显的抑制作用,移植瘤体积减小,差异有统计学意义(PVEGF-C启动子序列的低甲基化状态,抑制其蛋白表达,抑制胃癌的生长。

英文摘要

Objective To explore inhibitory effects of S-adenosylmethionine on vascular endothelial growth factor-C (VEGF-C) protein and cellular proliferation in gastric cancer by regulating methylation status of VEGF-C promoter. Methods MTT analyses and nude mice model were employed to examine the effects of S-adenosylmethionine on inhibiting gastric cancer growth In vitro and in vitro The protein expression of VEGF-C in gastric cancer cells was assessed by Western blot. The methylation status of VEGF-C promoter was assessed by bisulfite genomic DNA sequencing analysis. Results VEGF-C promoter was hypomethylated in MGC803 and SGC7901. The treatment of S-adenosylmethionine resulted in a heavy hypermethylation of VEGF-C promoter, which consequently down regulated protein level of VEGF-C. S-adenosylmethionine effectively inhibited the growth of gastric cancer cells In vitro and in vitro (P

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