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张永斌, 达明绪, 姚继彬等. S-腺苷蛋胺酸对VEGF-C表达及胃癌生长的影响[J]. koko体育app 学报（医学版）, 2015, 46(3): 384-388.
引用本文: 张永斌, 达明绪, 姚继彬等. S-腺苷蛋胺酸对VEGF-C表达爱及直肠癌植物的生长的危害[J]. 贵州大专学报（医药学版）, 2015, 46(3): 384-388.
ZHANG Yong-bin, DA Ming-xu, YAO Ji-bin. et al. S-Adenosylmethionine Inhibits Expression of Vascular Endothelial Growth Factor-C Protein and Cellular Proliferation in Gastric Cancer[J]. Journal of Sichuan University (Medical Sciences), 2015, 46(3): 384-388.
Citation: ZHANG Yong-bin, DA Ming-xu, YAO Ji-bin. et al. S-Adenosylmethionine Inhibits Expression of Vascular Endothelial Growth Factor-C Protein and Cellular Proliferation in Gastric Cancer[J]. Journal of Sichuan University (Medical Sciences), 2015, 46(3): 384-388.

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

  • 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。  
    Abstract: 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<0.05). Conclusion S-adenosylmethionine can effectively reverse DNA hypomethylation on VEGF-C promoter which down-regulates VEGF-C protein expression and inhibit gastric cancer growth.  
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