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VEGF-ASODN对唾液腺腺样囊性癌的影响

Inhibitory effect of VEGF antisense phosphorothioate oligodeoxynucleotides on the growth of human salivary adenoid cystic carcinoma xenografts in nude mice
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摘要 目的:研究血管内皮细胞生长因子反义寡核苷酸(VEGF-ASODN)对裸鼠荷人唾液腺腺样囊性癌的生长抑制作用。方法:20只BALB/c裸鼠随机分为4组,每组5只,实验1~3组建立人唾液腺腺样囊性癌荷瘤裸鼠移植瘤模型,并注射相应试剂。第4组为无荷瘤对照组。VEGF-ASODN组于瘤体及瘤周注射VEGF-ASODN 66μg。错义寡核苷酸组注射错义寡核苷酸66μg。生理盐水组注射生理盐水。每3 d 1次,共注射7次。实验结束后2 d,处死动物,取血清,测VEGF蛋白,测量肿瘤大小及重量,取肿瘤组织切片,免疫组化分析VEGF、PCNA、CD34表达,计算微血管密度(microvessel density,MVD)和增殖细胞核抗原标记指数(PCNA Label index,PLI),分子原位杂交检测VEGF mRNA表达。采用SPSS13.0软件包对数据进行统计学分析。结果:VEGF-ASODN组荷瘤裸鼠血清VEGF蛋白水平、肿瘤体积和重量、VEGF mRNA及其蛋白和PCNA、CD34表达均较对照组显著降低。结论:VEGF-ASODN通过抑制VEGF表达,从而抑制唾液腺腺样囊性癌细胞的生长。 PURPOSE :To investigate the inhibitory effect of VEGF antisense phosphorothioate oligodeoxynucleoiides on the growth of human salivary adenoid cystic carcinoma (SACC)xenografts in nude mice. METHODS: The VEGF-ASODN was synthesised artificially.After the model of human SACC xenografts in nude mice was established, they were randomly divided into three groups: antisense group, scrambled group and normal saline group. A control group without cancer was also established. Antisense(66 p^g), scrambled sequence(66 p^g ) and normal saline(once every 3 days and 7 times in all) were injected in three experimental groups, respectively. Two days after therapy, the mice were sacrificed. Serums were used for detection of VEGF protein. All tumors were measured and weighted. The quantity of VEGF mRNA and protein and PLI, MVD was detected by hybridization in situ and immunohistochemistry. SPSS13.0 software package was used for statistical analysis. RESULTS :The ~EGF-ASODN could suppress the expression of ~EGF in human SACC xenografts in nude mice and reduce VEGF protein in serum of nude mice significantly. It could also reduce the volume and weight of xenografts and could reduce the expression of VEGF mRNA and its protein, PCNA and CD34. CONCLUSION: By inhibiting the expression of VEGF, VEGF-ASODN can inhabit proliferation of human SACC xenografts in nude mice. Supported by Research Fund from Science and Technology Developmentt Plan of Shandong Province (2011GGH21822).
出处 《上海口腔医学》 CAS CSCD 北大核心 2012年第6期611-616,共6页 Shanghai Journal of Stomatology
基金 山东省科学技术发展计划资助项目(2011GGH21822)~~
关键词 血管内皮细胞生长因子 反义寡核苷酸 裸鼠 基因技术 唾液腺腺样囊性癌 VEGF ASODN Nude mice Gene therapy Salivary adenoid cystic carcinoma
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