Inhibition of tumor growth in xenograft nude mice model by recombinant adenovirus-mediated human endostatin gene therapy
- Author:
- No author available
- Journal Title:
- CHINESE JOURNAL OF RADIOLOGY
- Issue:
- 12
- DOI:
- 10.3760/j.issn:1005-1201.2003.12.003
- Key Word:
- 血管生成抑制剂;腺病毒,人;鼻咽肿瘤;疗效评价
Abstract： 目的观察重组人血管内皮抑素腺病毒(Ad/hEndo)在体内、体外的表达效率,以及对裸鼠移植瘤肿瘤血管生成的影响.方法携带人血管内皮抑素基因的新型重组腺病毒(Ad/hEndo)及携带β-半乳糖苷酶基因(LacZ基因)的重组腺病毒(Ad/LacZ)为自行构建.Ad/hEndo组(7只)瘤内注射1×109 空斑形成单位(pfu)的Ad/hEndo 100 μl,Ad/LacZ注射组(6只)瘤内注射1×109 pfu的Ad/LacZ注射100 μl,DMEM液注射组(5只)瘤内注射DMEM液100 μl,共注射5次.人鼻咽癌(CNE-2)和人脐静脉内皮细胞(ECV304细胞)被Ad/hEndo感染后,Western印迹和免疫酶联吸附法(ELISA)检测人血管内皮抑素蛋白的表达.CNE-2细胞株移植到裸鼠背脊部后,检测Ad/hEndo对鼻咽癌裸鼠移植瘤生长的抑制作用,微血管密度计数(microvessel density,MVD)分析Ad/hEndo对肿瘤血管生成的影响.结果 Western印迹和ELISA法检测到人血管内皮抑素基因在CNE-2和ECV304细胞高效表达.当感染复数(MOI)为20 pfu/细胞时,感染72 h后细胞培养上清中人血管内皮抑素蛋白浓度达588.34 ng/ml.Ad/hEndo可明显抑制鼻咽癌CNE-2裸鼠移植瘤生长,抑瘤率为46.43%(Ad/hEndo治疗组对腺病毒携带基因LacZ注射组,t=2.226,P<0.05)和49.70%(Ad/hEndo治疗组对DMEM液注射组,t=2.254,P<0.05).Ad/hEndo注射后3、7 d裸鼠血清中人血管内皮抑素蛋白浓度明显高于对照组.Ad/hEndo治疗组MVD为9.95 ± 2.20,对照组DMEM液注射组MVD为18.54 ± 1.80(t=7.158,P<0.05),说明Ad/hEndo明显抑制了肿瘤血管生成.结论腺病毒介导的人血管内皮抑素基因在体内、体外均获得高效表达,并明显抑制鼻咽癌CNE-2裸鼠移植瘤的肿瘤血管生成和肿瘤生长.
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