携带人内皮抑素基因的增殖型腺病毒AdTPHre—hE对胰腺癌的体内实验研究  

Therapeutic effects of replication-competent adenovirus carrying human endostatin gene on pancreatic cancer in mice

作　　者：方益锋[1] 单云峰[1] 罗定存[1] 张启瑜[1] 

机构地区：[1]杭州市第一人民医院肿瘤外科,310006

出　　处：《中华肝胆外科杂志》2011年第8期660-663,共4页Chinese Journal of Hepatobiliary Surgery

基　　金：基金项目：卫生部科研基金资助项目（WKJ2007-2-019）

摘　　要：目的 通过建立裸鼠胰腺癌肿瘤模型，在体内实验中进一步证实携带人内皮抑素基因的增殖型腺病毒AdTPHre-hE的抗肿瘤作用。方法 建立AsPC-1胰腺癌细胞BALB/c裸鼠皮下移植瘤模型，在瘤体内注射AdTPHre-hE治疗，观察肿瘤生长。ELISA法检测裸鼠血清中人内皮抑素浓度，肿瘤组织行Hexon 单克隆抗体免疫组化染色及微血管免疫组化染色。结果 AdTPHre-hE抑制肿瘤生长的作用显著强于Ad-hE（P〈0.01）和对照组（P〈0.01）。随着治疗时间的延长，裸鼠血清中内皮抑素表达量不断增加，明显高于Ad-hE组（P〈0.01）和对照组（P〈0.01）。病毒Hexon免疫组化染色显示,AdTPHre-hE治疗组移植瘤内可见片状或弥漫性分布的阳性染色，AdTPHre-hE治疗组瘤组织中微血管密度为16.3±4.3明显少于Ad-hE组的33.8±6.2（P〈0.01）和对照组的36.8±4.6（P〈0.01）。结论 增殖型腺病毒AdTPHre-hE介导人内皮抑素的表达，具有明显抑制肿瘤细胞生长的作用。Objective To establish human pancreatic cancer xenografts in nude mice, and to investigate the antitumor efficacy of human endostatin expressed by replication-competent adenovirus AdTPHre-hE in vivo. Methods Pancreatic cancer cells AsPC-1 were injected subcutaneously in BALB/c nude mice to establish the xenografts. Tumor growth was observed and measured after AdTPHre-hE treatment. Expression of endostatin was detected by ELISA assay. The tumors were harvested for pathologic examination and immunohistochemical staining. Results Tumors grew more slowly in the AdTPHre-hE group and their sizes were markedly smaller than those of the Ad-hE group（P〈0.01）and control group（P〈0.01）. Endostatin levels were detected in the sera of nude mice in all treated groups, and endostatin expression in AdTPHre-hE group increased with time. The endostatin level in the AdTPHre-hE treated group was much higher（P〈0.01）and increased faster than that in the Ad-hE treated group. Immunohistochemical staining for Hexon of adenovirus capsid showed more positive tumor cells in the tumor tissues treated with AdTPHre-hE. Immunohistochemical staining for FⅧ revealed a decreased microvessel density in the tumor tissues treated with AdTPHre-hE. Conclusion The replication-competent adenovirus efficiently expressed high-level endostatin and significantly inhibited tumor growth in vivo.

关 键 词：腺病毒 内皮抑素 胰腺癌 

分 类 号：R735[医药卫生—肿瘤]