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沉默血管内皮生长因子及促血管生成素-2基因抑制裸鼠人肺腺癌移植瘤生长的实验研究 被引量:3

Suppression of vascular endothelial growth factor and angiopoietin-2 to treat adenocarcinoma of lung
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摘要 目的研究沉默血管内皮生长因子(VEGF)及促血管生成素-2(Ang-2)基因表达对裸鼠人肺腺癌移植瘤生物学特性的影响。方法利用基因重组技术构建H1启动子驱动表达针对VEGF及Ang-2siRNA的重组腺病毒Ad-VEGFshRNA及Ad-Ang-2shRNA。制备裸鼠人肺腺癌A549细胞移植瘤模型,观察RNA干扰后(RNAi)对肿瘤生物学特性的影响。结果重组腺病毒接种裸鼠30d后,Ad-VEGFshRNA、Ad-Ang-2shRNA干扰组与对照组比较,肿瘤体积及重量均明显减小,差异均有统计学意义(P<0.01),并且Ad-VEGFshRNA及Ad-Ang-2shRNA联合干扰组与Ad-VEGFshRNA、Ad-Ang-2shRNA干扰组比较能够更有效地抑制肿瘤细胞的生长,差异有统计学意义(P<0.05);而Ad-VEGFshRNA组与Ad-Ang-2shRNA组比较差异无统计学意义(P>0.05)。免疫组织化学染色显示:Ad-VEGFshRNA、Ad-Ang-2shRNA干扰组细胞增殖减慢,凋亡增加,微血管密度明显少于对照组,差异有统计学意义(P<0.01)。并且Ad-VEGF shRNA及Ad-Ang-2shRNA联合干扰组与单基因干扰比较,能够更有效地抑制肿瘤细胞增殖,促进凋亡,差异有统计学意义(P<0.05)。结论 VEGF及Ang-2基因靶向RNA干扰在体内有明显抑制肺腺癌细胞生长的作用,联合抑制VEGF及Ang-2基因的表达能够更有效地抑制肺腺癌的生长。 Objective To investigate whether RNA interference could induce gene silencing in lung adenocarcinoma cells as well as assess the degree of vascular endothelial growth factor(VEGF) and angiopoietin-2(Ang 2) gene silencing and its effect on functional outcome.Methods Recombinant adenovirus Ad VEGF shRNA and Ad Ang-2 shRNA were constructed driving by H1 promoter targeted on VEGF and Ang-2 utilizing gene recombinant technology.A549 cells was transfected with recombinant adenovirus.30 nude rats were randomly divided into 5 equal groups to be transplanted with Ad VEGF shRNA-A549 cells,Ad Ang-2 shRNA-A549 cells,Ad VEGF shRNA add Ad Ang-2 shRNA-A549 cells;Ad null-A549 cells and PBS only as blank control group.The growth of glioma was observed every five day.Thirty days Later,the rats were killed and the tumors were taken out to be examined.The tumor volume and weight were measured.The tumors were excised for immunohistochemistral staining of FⅧ-related antigen,VEGF,Ang-2,PCNA and TUNEL.Results We successfully constructed recombinant adenovirus mediating Ad VEGF shRNA and Ad Ang-2 shRNA,the reproductive activity of the group transfected with Ad VEGF shRNA and Ad Ang-2 shRNA A549 cell was inhibited obviously.Comparing non-transfecting group and tranfecting Ad-Null group,they had significant difference(P< 0.01).The tumor volume and weight had statistical significance between the group treated by Ad VEGF shRNA/Ad Ang-2 shRNA or Ad-Null and PBS control group(P<0.01).Hemorrhage and lamellar necrosis were found in tumor treated by RNAi.Immunohistochemistral staining showed that the expression of Ang-2 and VEGF protein significantly decreased in the cancer cell treated by RNAi and meanwhile microvessel density decreased too.It also showed that apoptosis increased and cell reproductive activity was inhibited in the cancer cell treated by RNAi.Conclusions VEGF and Ang-2 may play an important role in lung adenocarcinoma progression.The specific small hairpin RNA targeting VEGF and Ang-2 can inhibit the expression of VEGF and Ang-
出处 《中华临床医师杂志(电子版)》 CAS 2011年第13期3756-3762,共7页 Chinese Journal of Clinicians(Electronic Edition)
基金 国家自然科学基金资助项目(30471718)
关键词 腺癌 血管内皮生长因子类 血管生成素2 腺病毒科 RNA干扰 Adenocarcinoma Vascular endothelial growth factors Angiopoietin2 Adenoviridae RNA interference
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