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[1] 达明绪[2] 姚继彬[2] 段耀星[2] 

机构地区：[1]宁夏医科大学临床医学院,银川750004 [2]甘肃省人民医院肿瘤外科,兰州730000

出　　处：《四川大学学报（医学版）》2015年第3期384-388,共5页Journal of Sichuan University(Medical Sciences)

基　　金：国家自然科学基金(No.30960371);甘肃省卫生行业科研计划项目(No.GSWST-09-11)资助

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、16mmol/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、4mmol/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〔192μmol/(kg·d)、768μmol/(kg·d)〕腹腔注射,对照组给予等量生理盐水腹腔注射,1次/d,15d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(P<0.05);VEGF-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(P<0.05)。结论 SAM可以改变胃癌细胞株MGC803和SGC7901中VEGF-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。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 Sadenosylmethionine on inhibiting gastric cancer growth in vitro and in vivo.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 vivo（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.

关 键 词：S-腺苷蛋胺酸 血管内皮生长因子-C 甲基化 胃癌 

分 类 号：R735.2[医药卫生—肿瘤]